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The  Future  Independence  and 
Progress  of  American  Medi- 
cine in  the  Age  of  Chemistry 

qA  ^port  by 

JOHN  J.  ABEL 

Professcr  of    Pharmacology,   Johns   Hopkins   Medical    School, 

iialtimore,  Md.     Editor,  Journal  Pharmacology 

and  Experimental  Therapeutics. 

CARL  L.  ALSBERG 

Diri'ctcr,   Food  Research   Institute,   Stanford   University,   Cal. 
Fonucrly    Chief    of    the    Bureau   of    Chemistry,    Depart- 
ment of  Agriculture.    Member,  Council  of  Pharmacy 
and  Chemistry,  American  Medical  Association. 

RAYMOND  F.  BACON 

Director,  Mellon  Institute  for  Industrial  Research, 
Pittsburgh,  Pa. 

F.  R.  ELDRED 

(  heniical  Consultant,  Eli  Lilly  &  Co.,  Indianapolis,  Ind. 

REID  HUNT 

1  rofessor  of  PharmacoloRy,  Harvard  Medical   School,  Bostor.. 

Mass.      Formerly    of    U.    S.    Public    Health    Service. 

President,  U.  S.  Phamacopceia  Conventiori. 

TREAT  B.  JOHNSON 

Professor  of  Organic  Chemistry,  Yale  University,  New  Haven, 
Conn. 

JULIUS  STIEGLITZ 

Chairman   Department   of   Chemistry,   University   of   Chicago, 
Chicago,   111.     Past   President,   American   Chemical   Society. 
Chairman,    Subcommittee    on    Synthetic    Drugs,    National 
Research    Council.      Vice-Chairman,    Council    of    Chem- 
istry  and    Pharmacy,   American    Medical   Association. 

F.  0.  TAYLOR 

Lhief  Lhemist,  Parke,  Davis  &  Co.,  Detroit,  Mich. 

CHARLES  H.  HERTY,  Chairman 

}  iitor,  Journal  of  Industrial  and  Engineering  Chemistry,  New 
York  City.     Past  President,  American  Chemical  Society. 


5 


>\ 


T177E  ask  the  careful  read- 
ing, discussion  and  con- 
sideration of  this  report  by 
physicians  and  surgeons,  by 
mothers  and  fathers,  by  edu- 
cators, hospital  directors  and 
trustees  and  all  others  whose 
hearts  are  interested  in  the 
welfare  of  the  future  genera- 
tions of  American  children. 


s:s 


FOREWORD 

This  report  is  the  outgrowth  of  an  editorial 
which  appeared  in  the  Journal  of  Industrial  and  En- 
gineering Chemistry  (September,  19 18),  pointing 
out  the  need  for  intensive  chemical  research,  under 
more  favorable  conditions  than  exist  today,  devoted 
to  the  alleviation  of  human  suffering.  The  ensuing 
discussion  led  to  the  appointment  of  a  committee  of 
the  American  Chemical  Society  in  January,  19 19, 
to  prepare  a  statement  of  plans  and  policies  for  the 
facilitation  of  research  in  this  field.  Since  that  date 
this  committee  has  held  frequent  meetings,  and  has 
had  the  cooperation  and  advice  of  leaders  in  the 
several  sciences  which  bear  upon  this  problem. 

In  order  that,  thvj  views  of  the  committee  and  the 
facts  upon  which-  they  are  based  should  be  made 
available  for  the  thoughtful  people  of  this  country, 
Tho  Chemical  Foundation,  Inc.,  arranged  for  the 
preparation  of  a  comprehensive  report  on  this 
subject. 

The  report  has  been  drafted  by  the  following  Sub- 
Committee:  Julius  Stieglltz,  Reid  Hunt,  Treat  B, 
Johnson,  F.  R.  Eldred  and  Charles  H.  Herty, 
Chairman. 

This  report  has  received  the  unanimous  approval 
of  the  following  committee : 


[a] 


John  J.  Abel 

Profesior'  of   Pharmacology,   Johns   Hopkins   Medical    School, 

Baltimore,  Md. 
Editor,  Journal  Pharmacology  and  Experimental  Therapeutics 

Carl  L.  Alsberg 

Director,  Food  Research  Institute,  Stanford  University,  Cal. 

Formerly  Chief  of  the  Bureau  of  Chemistry,  Department  of 
Agriculture 

Member,  Council  of  Pharmacy  and  Chemistry,  American  Medi- 
cal Association 

Raymond  F.  Bacon 

Director,  Mellon  Institute  for  Industrial  Research,  Pitts- 
burgh, Pa. 

F.  R.  Eldred 

Chemical   Consultant,   Eli   Lilly  &   Co.,   Indianapolis,   Ind. 

Reid  Hunt 

Professor   of   Pharmacology,    Harvard    Medical    School,   Bos- 
ton, Mass. 
Formerly  of  U.  S.  Public  Health  Service 
President,  U.  S.  Pharmacopoeia  Convention 

Treat  B.  Johnson 

Professor  of  Organic  Chemistry,  Yale  University,  New  Haven, 
Conn. 

Julius  Stieglitz 

Chairman,  Department  of  Chemistry,  University  of  Chicago, 
Chicago,  111. 

Past  President,  American  Chemical  Society 

Chairman,  Subcommittee  on  Synthetic  Drugs,  National  Re- 
search Council 

Vice-Chairman,  Council  of  Chemistry  and  Pharmacy,  American 
Medical  Association 

F.  O.  Taylor 

Chief  Chemist,  Parke,  Davis  &  Co.,  Detroit,  Mich. 

Charles  H.  Herty,  Chairman 

Editor,    Journal    of    Industrial    and    Engineering    Chemistry, 

New  York  City 
Past  President,  American  Chemical  Society 

[3] 


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INTRODUCTION 

„  I  r      L         When  It  became  clear  during  the 

Research  for  the  ,  .  *=* 

J  t    W  recent  war  that  poisonous  gas  was 

to  constitute  an  important  muni- 
tion, our  country  called  to  Its  service  a  great  group 
of  Its  ablest  research  chemists  to  provide  efficient 
means  of  defense  and  to  solve  those  problems  of  pro- 
duction which  would  provide  our  field  forces  with 
an  ample  supply  of  this  new  weapon. 

Not  to  the  professional  inventor  nor  to  the  acci- 
dent of  haphazard  discovery  was  this  grave  respon- 
sibility assigned,  but  to  the  trained  workers  in  sys- 
tematic research.  Nor  were  these  men  asked  to 
undertake  this  vital  work  In  the  seclusion  and  Isola- 
tion of  their  respective  laboratories  but  they  were 
assembled  at  the  American  University  Experiment 
Station  on  the  outskirts  of  the  city  of  Washington, 
under  one  roof  as  it  were,  where  by  daily,  nay  hourly, 
conference  utmost  speed  could  be  secured  in  the  solu- 
tion of  those  problems  on  which  the  question  of  life 
and  death  so  closely  hung. 

But  these  chemists  found  that  they  alone  were 
inadequate  for  the  task.  To  supplement  their  spe- 
cial skill  and  knowledge  there  were  added  to  the 
staff  pharmacologists  and  experimental  pathologists. 

Through  the  combined  efforts  of  these  groups, 
working  in  closest  association  and  provided  with 
ample  facilities  for  research,  results  were  accom- 
plished with  a  speed  and  certainty  which  amazed  all. 
The  paths  to  agencies  for  both  defense  and  offense 

[5] 


?  •:  •• 


were  clearly  pointed  out  and  large  scale  production 

quickly  followed. 

rpi,    u  „,  Is  there  no  valuable  lesson  for 

1  he  tSatUe  .       ,  .        .    ,  .  .  . 

.     .  peace  in  this  mighty  and  successful 

j^.  effort  in  the  making  of  war?     Is 

there  not  another  battle  constantly 
to  be  fought — the  battle  against  disease?  While  war 
claims  its  sacrifice  in  millions  of  lives,  disease  each 
year  claims  its  tens  of  millions.  Pneumonia,  influ- 
enza, tuberculosis,  cancer,  meningitis,  malaria,  epi- 
lepsy, insanity,  feeble-mindedness,  malnutrition, 
abnormal  development,  and  a  multitude  of  other 
diseases  claim  their  many  victims.  And  what  a  host 
of  wounded  do  we  have  in  this  destructive  war  of 
peace — men,  women,  and  children  who  suffer,  often 
longing  for  death  as  a  relief,  their  efficiency  crippled 
and  their  future  on  earth  beclouded  I 

Can  we  not  bring  to  these  problems  the  same 
methods  so  successfully  employed  in  the  solution  of 
means  of  making  war?  The  experience  of  the  ages 
is  now  being  drawn  upon  in  this  fight  against  disease, 
but  the  means  are  entirely  inadequate  as  shown  by 
the  continued  ravishment  of  disease.  Too  often,  in 
default  of  exact  knowledge,  we  blindly  seek  remedial 
agencies.  The  annual  drug- bill  of  this  nation  is  in 
round  numbers  $500,000,000,  of  which  amount 
$300,000,000  is  spent  for  so-called  patent  medicines. 
The  number  of  medicaments  is  increasing  at  a  tre- 
mendous rate,  beyond  all  proportion  to  the  amount 
of  systematic  research  being  devoted  to  the  subject. 
Thirty  years  ago  2,699  <^rug  items  were  reported  to 
be  on  the  market;  today  more  than  45,000  are  said 
to  be  in  use.  The  frailties  and  suffering  of  humanity 
are  being  grossly  exploited. 

[6] 


,,  J.  .  Several  centuries  ago  the  chem- 

Medicme         ,  ,     ,         ,      .  .    ^       „         ,    , 

^,  ist  and  the   physician   cooperated 

^,       .  _         closely  for  the  alleviation  of  suffer- 
Chemistry  ^.        ,  .   r     •         r    i 

ing;  the  chier  aim  or  chemistry  m 

those  days  was  the  providing  of  mediclnals  for  the 
use  of  the  physician.  Then  the  physician  and  the 
chemist  separated,  the  physician  looking  more  and 
more  to  other  means  to  effect  his  ends,  while  the 
chemist  turned  to  the  production  of  wealth  in  the 
industries,  as  illustrated  by  the  pioneer  work  of 
Agrlcola  on  metallurgy,  a  work  recently  translated 
and  edited  by  Mr.  and  Mrs.  Herbert  Hoover.  Later 
the  physician  turned  back  somewhat  to  his  former 
aid  and  found  most  useful  substances  awaiting  him. 
For  instance,  ether  had  been  discovered  in  the  thir- 
teenth century,  but  its  value  as  an  anaesthetic  was  not 
definitely  recognized  until  1846.  During  the  inter- 
vening ^vc  or  six  hundred  years  untold  suffering 
resulted  from  lack  of  knowledge  of  Its  application 
in  producing  insensitlveness  to  pain.  Magnesium 
sulphate  was  well  known  to  chemists  in  1694,  but 
two  hundred  years  elapsed  before  It  was  learned 
what  great  relief  it  gave  in  lockjaw,  burns,  and 
strychnine  poisoning.  Twenty-three  years  elapsed 
betwxen  the  discovery  of  amyl  nitrite  by  the  chemist 
and  the  discovery  of  Its  medicinal  properties  by  the 
physician;  during  this  period  tens  of  thousands  of 
human  beings  suffered  the  tortures  of  angina  pectoris 
because  the  chemist,  pharmacologist  and  physician 
were  not  working  together. 

j,i  There  has  been  a  return  to  the 

„  earlier  views  as  to  the  relation  of 

^,      .    ,        chemistry  to  medicine,     liach  hu- 

Factory  ^^^  ^^^^  ^^  "°^  recognized  to  be 

a   chemical   factory  in  which   the 

most   complicated   chemical    and   physical   changer 

[7] 


are  continuously  taking  place.  When  these  re- 
actions are  normal  from  day  to  day,  we  are  in 
good  health.  When  they  are  abnormal,  they  are 
a  direct  cause  of  disease,  as  in  gout,  diabetes, 
goiter,  and  other  serious  diseases.  Moreover, 
when  abnormal,  these  fundamental  chemical  reac- 
tions lower  the  natural  resistance  of  the  body, 
especially  to  invading  disease  germs,  and  they  thus 
lead  indirectly  to  infection,  disease  and  death.  Thus, 
it  is  well  known  that  the  chief  danger  to  the  diabetic 
patient  under  proper  medical  care  is  found  in  his 
abnormally  low  resistance  to  infection  as  the  result 
of  the  inability  of  the  body  to  maintain  its  normal 
chemical  reserve.  Even  the  invading  disease  germs 
in  most  cases  carry  out  their  fell  work  through  chem- 
ical agencies,  through  the  production  of  potent 
poisons  (toxins)  acting  on  the  heart,  the  respiratory 
nerve  centers,  or  some  other  vital  organ,  or  grad- 
ually poisoning  the  whole  system. 

^,       .  ^  The  bacteriologist  and  patholo- 

Cnemistry  .      ,  i  •  i     i  i         • 

M    «  S  Z  ^^^^  nave  accomplished  wonders  m 

p    ,j  the  present  and  the  last  generations 

in  tracing  the  living  carriers  of  the 
great  infectious  diseases,  and  the  world  owes  our 
Pasteurs,  Kochs,  Behrings,  Flexners  and  many 
other  valiant  workers  with  these  deadly  carriers 
of  disease  a  debt  of  eternal  gratitude.  But  the 
fact  is  that  bacteriologist  and  pathologist  have 
now  definitely  reached  the  point  where  they  must 
turn  to  chemistry  for  the  solution  of  many  of 
their  most  important  problems.  As  an  illustration: 
their  antitoxins,  their  most  powerful  weapons  in  com- 
batting invading  germs,  are  chemical  substances  of 
specific  curative  power  but  of  unknown  composition 
and  never  isolated  as  yet  as  pure  principles.     They 

[8] 


are  always  Injected  Into  our  bodies  in  the  form  of 
crude  mixtures,  loaded  down  with  undesirable  and 
to  some  extent  even  harmful  ingredients.  The  Isck 
lation  of  the  pure  principles  by  chemical  methods, 
supplementing  the  pioneer  work  of  bacteriologist  and 
pathologist,  would  prove  one  of  the  greatest  ad- 
vances in  medicine,  giving  the  practitioner  the  power 
to  combat  an  infection  by  swift,  exact  and  sufficiently 
powerful  doses,  where  now  he  often  acts  with  hesi- 
tation and  misgiving.  Another  Instance:  coopera- 
tion of  the  medical  investigator  with  the  chemist 
(Dr.  John  Howland  and  his  collaborators)  has  re- 
cently led  to  the  recognition  of  the  fact  that  in 
rickets,  the  scourge  of  many  thousands  of  children, 
there  is  a  deficiency  of  such  common  chemical  com- 
ponents as  lime  and  phosphate  In  the  blood — a  dis- 
covery that  by  the  same  cooperation  must  ultimately 
lead  to  successful  preventive  methods.  But  hew 
long  must  the  thousands  of  little  victims  wait  for 
relief? 

In  the  ultimate  cell  Itself,  In  the  protoplasm  of 
that  cell,  chemical  reactions  take  place  which  In  a 
fundamental  way  determine  health  or  sickness — and 
of  these  reactions  we  know  but  little. 

rp.  How  can  chemistry,  cooperating 

^,      .  .         now  with  medicine  as  It  cooperated 
J.,  with   the   war   and  naval   depart- 

ments,   help    best    In    this    battle 
against  disease? 

First — The  chemist  is  being  called  upon  for  the 
preparation  of  specific  medicaments  for  the  cure  or 
alleviation  of  specific  diseases.  Salvarsan  ("606^'), 
the  product  of  chemical  research  in  cooperation  with 
medicine,  has  done  more  In  four  years  for  the  elimi- 
nation of  syphilis  than  was  accomplished  in  four  cen- 

[9] 


turies    of    hygiene    and    education.      So,    too,    the 

naturally  occurring  cocaine,  so  valuable  as  a  local 

anaesthetic  and  yet  so  often  poisonous,  has,  by  careful 

chemical  study,  been  found  to  be  a  very  complex 

chemical  compound,  to  only  certain  parts  of  which 

was  to  be  ascribed  its  beneficent  anaesthetic  effect, 

other  parts  carrying  useless  poisonous  qualities  of 

no  value  to  man.    Thus  was  the  chemist  enabled  to 

improve   on   nature,    and   there   resulted   procaine, 

better   than   cocaine   because    equally   good    as    an 

anaesthetic    and    yet    without    secondary    poisonous 

characteristics.     Today   a   modification   of  quinine 

gives  promise  as  a  specific  cure  of  pneumonia;  It 

destroys  the  pneumococcus  germs  in  glass  vessels, 

but  it  is  still  too  poisonous  to  be  used  in  sufficient 

strength  to  combat  the  hosts  of  invading  germs  in  the 

human  body  stricken  with  pneumonia. 

r»-  7j  »•  t  So,  too,  the  study  of  the  pure 

Field  Rich  .     •   ,  r  r 

.    n       •  pnnciples  or  our  organs  or  secre- 

171  Promise        \         ^  r  i  j    •  i   • 

tion  opens  up  a  held  rich  in  promise. 

The  isolation  and  study  of  epinephrine  (adrenalin) 
has  furnished  a  means  of  relieving  the  intense  suffer- 
ing of  acute  bronchial  asthma,  of  checking  hemor- 
rhage and,  used  under  proper  conditions,  of 
carrying  the  strained  heart  through  the  shock  of 
operation,  the  critical  stages  of  pneumonia.  The 
isolation  of  the  active  principle  of  glands  controlling 
normal  growth,  of  those  of  digestion  and  metabol- 
ism, of  antitoxins,  vaccines,  serums,  etc.,  as  men- 
tioned above,  all  await  the  hands  of  the  chemist  and 
when  isolated  and  prepared  pure  will  place  in  the 
hands  of  physicians  material  which  can  be  adminis- 
tered with  absolute  accuracy  and  which  gives  promise 
of  instantaneous  effect  by  hypodermic  injection. 
Second — Life  Is  dynamic,  not  static;  and  so  the 
[10] 


physical  chemist  must  be  called  into  active  partici- 
pation in  this  work.  The  matter  of  health  is  closely 
bound  up  in  the  delicate  adjustment  of  speed  of  the 
various  chemical  reactions  taking  place  in  the  body. 
These  reactions  may  be  accelerated  or  retarded  by 
minute  quantities  of  catalyzers  (enzymes,  such  as 
pepsin) .  So,  too,  the  brilliant  advances  by  physical 
chemists  in  the  study  of  colloids  have  found  as  yet 
but  imperfect  application  to  the  problems  of  the 
body,  where  in  nerve  and  cell,  muscles  and  organs, 
the  questions  to  be  dealt  with  are  largely  those  of 
colloidal  chemistry. 

^  ..         .  These  complex  problems  of  the 

Cooperating       .      ,  \    ^   S  ,  ,.  . 

e  .  body  are  too  mnnitely  complicated 

jciencGS 

to  be  solved  by  any  one  class  of 

scientists.  Preeminently  chemical  in  their  nature, 
the  chemist  alone  is  imperfectly  equipped  to  carry 
them  to  complete  and  successful  solution.  He  must 
join  hands  with  the  pharmacologist,  the  pathologist 
and  the  experimental  biologist.  For  that  reason 
much  of  the  work  in  progress  today  is  halting  and 
uncertain.  In  a  few  institutions  such  cooperation  is 
had,  though  too  often  the  chemist  plays  the  minor 
role.  In  our  universities  constant  work  is  in  progress 
and  should  be  generously  supported,  but  too  often 
the  workers  are  isolated  and  with  only  part  time  to 
devote  to  research  because  of  the  claims  of  teaching 
duties.  Too  often  the  chemist  needs  the  knowledge 
and  technique  of  the  biologist,  and  equally  often  the 
biologist  needs  the  chemist's  information  and  point 
of  view.  But  the  lesson  of  the  war  is  before  us  and 
we  know  what  great  results  may  be  expected  of 
cooperation  under  ideal  conditions  of  time  and  equip- 
ment for  research.     Is  not  the  battle  against  disease 

[11] 


much  more  imperative  in  its  call  than  the  battle  of 

man  against  man? 

^    ,     ,  But  the  latter  war  was  carried 

Outlet  for  J  ,         , 

p       .    ,        out  under  government  control,  and 

y ,    ,.  since  all  are  subject  to  disease  it 

may  be  argued  that  the  prosecution 
of  similar  work  in  times  of  peace  should  be  a  gov- 
ernment undertaking,  just  as  fire  control  is  a  com- 
mon tax  upon  the  inhabitants  of  a  municipality.  It 
has  been  contrary,  however,  to  the  practice  of  our 
legislators  to  provide  means  for  carrying  on  funda- 
mental scientific  research  in  government  laboratories. 
Such  laboratories  exist  for  the  enforcement  of  laws 
or  for  other  utilitarian  purposes  rather  than  for  the 
prosecution  of  fundamental  research.  In  peace  the 
desire  is  to  get  away  from  government  control. 

Nor  can  the  manufacturers  of  drugs  be  looked  to 
for  the  carrying  out  of  any  such  undertaking.  The 
results  of  this  work  will  doubtless  be  the  elimination 
of  many  ineffective  drugs  now  manufactured,  while 
for  those  which  persist  the  actual  amounts  to  be 
manufactured  are  too  small  to  attract  capital  to  its 
support. 

If  such  work  is  to  be  successfully  prosecuted  in 
our  midst,  it  must  be  through  the  practical  idealism 
of  America,  which  can  here  find  abundant  outlet  in 
providing  such  conditions  as  will  direct  the  future 
energies  of  chemistry  in  America  to  this  greatest 
blessing  to  mankind,  a  blessing  which  will  not  be 
confined  to  its  own  borders,  but  which  will  stretch 
out  its  helping  hands  to  all  suffering  humanity. 


[12] 


THE  RELATION  OF  THE  FUNDAMENTAL 
SCIENCES  TO  MEDICINE 

^,       .  ,  Chemistry    is    the    fundamental 

Chemistry  .               ^     i                 r            •            r 

T  ni     '  science   of   the   transformation    of 

and  Fhysics  t^i      .      •      i      r       i               i 

and  Li  matter.   Physics  is  the  fundamental 

science  of  the  transformation  of 
energy  or  power  to  do  work.  Life  in  ail  of  its 
forms,  from  its  beginning  to  its  end,  Is  the  highest, 
most  complex  expression  of  the  transformation  of 
matter  and  of  the  transformation  of  energy.  In 
these  direct  statements — which  will  be  presently  elu- 
cidated by  being  considered  from  various  points  of 
view — we  have  the  key  to  the  trend  of  the  most 
important  phases  of  modern  medical  research,  to 
the  faith  of  a  large  group  of  scientific  men  in  its 
future. 

Need  for  ^^  ^^  ^  ^^^^  daily  becoming  more 

Concerted        impressive,    that  medicine   by   the 
Attack  ^^^y  force  of  the  fundamental  na- 

ture of  life  in  Its  material  aspects, 
is  turning  more  and  more  to  chemistry  and  to  phys- 
ics for  the  final  solution  of  many  mighty  and  per- 
plexing problems  of  the  prevention  and  cure  of 
disease.  Thus  the  great  British  physiologist  Bayliss 
says  in  the  Introduction  to  General  Physiology 
(19 19):  "As  physiologists,  our  task  is  to  refer, 
as  far  as  we  can,  all  phenomena  of  life  to  the  laws 
of  physics  and  chemistry."  By  the  same  token, 
there  is  no  undertaking  which  could  hold  out 
greater  promise  of  positive  and  far-reaching  results 

[13] 


in  almost  every  branch  of  medicine  than  concerted 
attack  upon  its  problems  by  the  close  cooperation  of 
expert  chemists,  expert  physicists,  expert  biologists 
and  medical  men  organized  on  the  basis  of  this  fun- 
damental point  of  view :  that  life  is  the  most  complex 
expression  of  the  transformation  of  matter  and 
energy  and  that  chemistry  and  physics  are  the  funda- 
mental sciences  of  the  transformation  of  matter  and 
energy.  There  is  at  present  in  this  country  no  re- 
search center  organized  for  such  an  attack  by  closest 
cooperation  under  the  leadership  of  these  fiinda- 
mental  sciences.  The  urgent  need  for  such  an  or- 
ganization should  become  apparent  from  a  more 
detailed  consideration  of  the  propositions  just  now 
laid  down. 

Medicine  is  concerned  with  the  preservation  of 
life  and  we  will  first  examine  in  a  brief  survey  the 
problem  of  life  from  its  material  side,  which  forms 
the  foundation  of  medical  science.  We  will  then 
consider,  again  briefly,  what  chemistry,  and  to  a  cer- 
tain extent  physics,  are  chiefly  concerned  with,  and 
we  will  thus  be  prepared  finally  to  turn  to  the  main 
part  of  our  study,  the  consideration  of  the 'specific 
ways  in  which  the  fundamental  sciences  are  needed 
to  serve  the  science  of  medicine,  the  consideration 
of  some  of  the  great  specific  problems  which  chem- 
istry and  physics  must  solve  for  medicine. 

I.    Living  Organisms  Are  Chemical  Laboratories 

J.,  What  justification  have  we  for 

Life  -  .  .,-... 

T  /^L      •    f      the  sweepmg  assertion  that  lire  m 
Is  Chemical         n   •       r  i      •  11 

J    .  .  all  Its  rorms,  be  it  vegetable,  ani- 

mal or  human,  is  the  highest  ex- 
pression of  the  transformation  of  matter  and  of 
energy?     When  we  plant  seeds  in  the  fertile  soil, 

[14] 


the  first  stage  of  development  consists  in  the 
transformation  with  the  aid  of  water  of  the  food, 
starches,  proteins,  fats,  stored  in  the  seed  itself, 
into  rootlets,  striking  down  into  the  soil  below, 
and  into  stem  and  stalk,  striking  upward  to 
reach  finally  the  free  air  above.  From  the  soil  the 
rootlets  absorb  water  and  mineral  salts — potash, 
lime,  sulphates,  phosphates,  nitrogen  in  the  form  of 
nitrates  and  ammonia ;  from  the  air  above  the  grow- 
ing plant  absorbs  and  transforms  with  the  aid  of  the 
energy  of  sunlight  carbon  dioxide,  the  waste  product 
of  all  animal  life  and  of  our  cities*  furnaces.  From 
these  simple  ingredients  thus  taken  from  soil  and 
air,  the  plant  manufactures  an  infinite  variety  of 
new  chemical  substances.  Including  carbohydrates 
(starches,  sugars,  gums,  cellulose,  wood),  proteins, 
fats  and  oils,  alkaloids  (quinine,  strychnine,  mor- 
phine), dyes,  and  Innumerable  other  substances.  We 
have  here  in  our  growing  plants  tremendously  In- 
tensive and  infinitely  varied  chemical  laboratories, 
on  the  output  of  which  all  animal  life  and  in  par- 
ticular all  human  life  is  finally  dependent  for  its  very 
existence. 

Chemists  ^^  ^^  ^^^^  known  that  the  careful 

Heln  guidance  of  the  chemist  in  the  study 

Agriculturists  °^  ^^^  f'\  'P-  *f  Providing  of 
proper  food  for  the  plant  in  the 
form  of  fertilizers,  nitrates,  ammonia,  potash,  phos- 
phates— has  made  it  possible  to  multiply  the  yield  of 
our  acres  at  small  cost  by  intensive  cultivation;  but 
this  is  only  a  small  fraction  of  what  the  chemist  has 
done,  is  doing  and  will  do  in  raising  agriculture  and 
forestry,  with  the  aid  of  the  expert  botanist,  from 
arts  to  the  level  of  exact  sciences — with  untold  benefit 
to  mankind. 

[15] 


j^.  J  Human  life,  like  all  animal  life, 

^  ,,  quite  obviously,  is  also  dependent 

^j       .    1  J. J     in  its  every  instant  on  the  chemical 
LlieniicaL  Aid  .         -'  .  .  . 

transformation    of    matter:    from 

our  inception  to  our  return  to  dust,  we  are  trans- 
forming carbohydrates,  fats,  proteins,  salts,  water; 
every  breath  we  draw,  every  motion  we  make  in- 
volves chemical  combustion.  The  assimilation  of 
our  food,  its  proper  utilization,  its  proper  elimina- 
tion, every  single  function  indeed  of  our  life  is  de- 
pendent on  definite  chemical  and  physical  processes. 
No  wonder,  indeed,  is  it  that  ultimately  it  is  the 
chemist  and  the  physicist  who  are  called  to  his  assist- 
ance by  the  watchful  guardian  of  these  complex 
chemical  laboratories,  the  medical  practitioner,  in 
the  search  for  the  final  exact  knowledge  for  the 
proper  control  of  the  healthy  functioning  of  life. 
Indeed,  so  profound  are  these  relations  that  even 
the  ultimate  questions  of  life,  of  paramount  moment 
to  the  race,  the  fertilization  of  the  seed,  the  enliven- 
ing of  the  ovum — so  like  the  kindling  of  a  flame — 
the  problems  of  heredity,  of  transmission  of  race 
and  character  from  generation  to  generation — all 
these  great  questions  are  being  recognized  as  funda- 
mental problems  for  whose  answer  biology  has  at 
length  called  in  the  aid  of  chemistry. 

^,       .  It  is  not  surprising — as  pointed 

Tr  J    7-  evidences  of  the  modern  trend — 

Underlies  i         i      t  t     i       i       i 

ni  J'    7  c      •       that  leading  medical   schools   are 
Medical  bervice   .  .         ^  ,     ,  r  u  ^i_ 

increasing  two  and  three  rola  the 

preparation  in  these  fundamental  sciences  and 
especially  in  chemistry,  demanded  of  students  for 
admission  to  their  classes;  It  is  not  surprising  that 
pioneer  medical  men,  engaged  In  research,  are  re- 
turning in  numbers  to  our  universities  to  study  more 

[16] 


and  still  more  chemistry  and  physics  as  they  find 
them  absolutely  essential  to  the  proper  development 
of  their  investigations.  There  is  no  more  over- 
loaded  student  than  the  medical  student  of  today, 
there  is  no  more  taxed  professional  man  than  the 
successful  physician —  and  if  these  men,  in  the  face 
of  extreme  demands  on  their  time  and  strength,  de- 
vote ever  more  of  this  precious  time  to  the  study 
of  the  fundamental  sciences  or  chemistry  and 
physics,  there  must  indeed  be  an  urgent,  compelling 
force — and  that  Is  simply  the  ever-increasing 
recognition  of  the  fact  that  life  has  its  abode  In  a 
highly  complex  laboratory  controlled  by  chemistry 
and  physics. 

.     .  In  this  trend  of  recent  years  it 

Ancient  .        .  .                                   ,       •' 

^           .  ,     IS  or  mterest  to  note  that  we  are 

Connection  of  ,                     .                 ,             |.     ^ 

,,   ,.  .  but  returnmg  to  the  earliest  con- 

Meaicme  .                    F  ,      .     .                ,     . 

,  sciousness  or  the  mtimate  relations 

^,       .  between   chemistry   and   medicine. 

Indeed,  the  very  name  chemistry 
refers  to  the  land  of  ChemI  (Egypt)  where  chem- 
istry originated  in  the  temples  In  which  priests  ex- 
perimented with  simple  chemicals  for  the  prepara- 
tion of  medicinals.  For  many  centuries  indeed  the 
connection  between  medicine  and  Its  daughter  science 
chemistry  was  so  close  that  In  the  sixteenth  century 
the  great  physician  and  chemist  Paracelsus  stated  that 
"the  true  purpose  of  chemistry  Is  not  to  make  gold, 
but  to  prepare  medicines."  How  fruitful  this  con- 
ception was  In  the  hands  of  Paracelsus  Is  shown  by 
the  fact  that  he  Introduced  into  medicine  the  use  of 
mercury,  lead,  sulphur.  Iron,  arsenic,  copper  sulphate, 
laudanum — some  of  the  drugs  most  valued  at  the 
present  day.  But  In  spite  of  this  valiant  protest  of 
Paracelsus,  chemistry  drifted  away  from  medicine, 

[17] 


first  in  the  effort  to  make  gold  by  the  conversion  of 
baser  metals,  later  in  the  much  more  successful  ef- 
forts to  create  riches  by  the  application  of  chemistry 
to  industrial  processes,  for  most  of  our  great  modern 
industries,  from  the  making  of  steel  and  iron  to  the 
manufacture  of  dyes,  are,  indeed,  in  largest  measure 
based  on  chemical  processes.  It  is  noteworthy,  too, 
that  the  comparatively  recent  return  of  chemistry  to 
the  service  of  medicine  was  signalized  at  the  outset 
by  Chemistry's  gift  to  Medicine  of  Pasteur,  one  of 
the  great  founders  of  modern  medicine  and  one  of 
the  greatest  benefactors  of  the  human  race. 

II.     How  Chemistry  Attacks  Its   Great  Problems 

If  we  turn  now  to  the  consideration  of  what  chem- 
istry is  occupied  with,  its  role  of  the  fundamental 
science  of  the  transformation  of  matter,  we  will 
more  clearly  perceive  exactly  how  it  can  and  must 
serve  as  the  handmaiden  of  medicine.  In  their 
efforts  to  understand,  indeed  to  master  the  trans- 
formation of  matter,  chemists  have  followed  two 
great  lines  of  attack:  in  both  of  these  chemistry  has 
aimed  to  be  an  absolutely  exact  science,  as  exact, 
indeed,  as  mathematics — so  that  it  may  attain  its 
objects  with  the  accuracy  and  reliability  with  which 
we  can  be  sure  that  two  and  tw^o  make  four.  The 
first  of  these  lines  of  attack  is  what  we  shall  call  the 
structural  side — the  discovery  and  study  of  the  way 
in  which  substances  are  put  together  or  constructed; 
the  second  line  of  attack  we  may  call  the  functional 
side — the  discovery  and  study  of  the  laws  controlling 
the  way  in  which  substances  act  upon  one  another. 

We  may  compare  these  two  lines  of  attack  with 
the  way  in  which  visitors,  say  from  Mars,  would  study 
what  would  be  to  them  the  mysteries  of  our  terres- 

[18] 


trial  civilization.  For  instance,  in  a  study  of  New 
York  City  a  whole  group  of  Martian  architects 
would  be  kept  busy  examining  minutely  the  mode  of 
construction  of  the  sky-scrapers  from  their  deep-set 
foundations,  through  the  steel  skeletons,  to  their 
thousand  elaborate  details  of  utility,  convenience 
and  decoration ;  they  would  study  the  construction  of 
residences,  apartment  houses,  tenements,  bridges, 
streets,  railways,  subways.  But  quite  another  group 
of  men  would  be  especially  devoted  to  the  study  of 
the  laws  governing  the  streams  of  life  pouring 
through  these  structures,  banks,  post-offices,  fac- 
tories, subways,  and  hundreds  of  other  units  of  the 
great  life  of  the  city  In  the  act  of  functioning. 

Constructive      ,.  ^^^""^   "f    fi«t   the    structural 
Ch      '  try  ^^        attack  by  chemistry  m  the 

D      J  Study    of    the    transformation    of 

iSasea  on  •'  r    i    i         i        • 

-*.  matter,  we  find  that  chemistry  aims 

Analysis  ^^  analyze  every  material  that 
comes  under  its  ken  in  the  most 
minute  fashion.  It  first  separates  and  isolates  the 
pure  principles,  scores  of  which  may  compose  a  mix- 
ture such  as  our  blood.  It  studies  the  properties 
of  these  pure  principles  minutely  and  then  It  pro- 
ceeds even  to  a  far  finer  analysis;  It  takes  these  pure 
principles  apart  to  their  very  atoms^ — indeed  It  Is 
now  engaged  In  dissecting  and  analyzing  the  very 
atoms  themselves — exactly  as  a  bright-minded  boy 
would  take  his  watch  apart  to  the  last  screw  and 
wheel  or  his  auto-engine  to  the  last  bar  and  nut. 
This  ultimate  or  molecular  analysis,  as  we  call  it, 

*Thus,  the  smallest  particle  of  water  (its  "molecule")  is  found 
to  contain  one  atom  of  oxygen  combined  with  two  atoms  of  hydro- 
gen and  chemists  express  its  "structure"  by  the  formula  H-O-H. 
Most  important  principles  have  far  more  complex  structures  (see 
below). 

[19] 


can  satisfy  only  in  part  the  chemist's  unconquerable 
determination  to  know  all  about  the  thousands  of 
principles  he  is  able  to  isolate  in  this  world  of  ours; 
for  having  taken  the  molecules  of  important  prin- 
ciples apart  and  studied  how  atom  is  united  to  atom, 
often  dozens  of  them  in  a  single  molecule,  he  does 
not  rest  until  he  has  succeeded  in  reconstructing 
(synthesizing)  perfectly  his  principles^ — very  much 
as  the  ambitious  boy  will  not  rest  until  he  has  recon- 
structed his  watch  or  his  auto-engine.  Having  thus 
acquired  complete  knowledge  of  the  ground  plan  of 
important  principles  which  we  find  in  nature,  the 

^     ,.  chemist  in  many  an   instance   has 

Creative  r         i    •  -i  i 

Ch      '  tr         lound  It  possible   to   improve  on 

nature  and  construct  more  perfect 

principles — exactly  as  In  the  experience  of  the  writer, 

lads  taking  the  engine  of  a  motor  boat  apart  were 

able   by  ingenious   Improvements  to  reconstruct  it 

with  an  Increase  In  Its  speed  and  power  of  20  to  25 

*Thus  Baeyer  showed  that  indigo  has  the  structure. 


0=0 


H 


H  H 


H 


VV" 


H         H 


The  letters  C,  H,  O  and  N  signify  atoms  of  carbon,  hydrogen, 
oxygen  and  nitrogen,  and  the  lines  joining  them  show  how  the 
atoms  are  linked  up  in  the  molecule.  It  took  fourteen  years  for 
Baeyer  to  solve  this  problem — with  the  result  ultimately  that  Ger- 
many succeeded  in  making  real  indigo  out  of  coal  tar  of  an  annual 
value  of  millions  of  dollars, 

[20] 


per  cent — exactly,  indeed,  as  human  intelligence  has 
always  improved  on  nature,  leading  the  race  from 
gloomy,  damp  and  uncomfortable  caves  to  houses 
growing  ever  more  perfect  and  convenient,  improv- 
ing the  quality  of  animals  by  domestication,  raising 
the  yield  of  the  soil  by  fertilization,  and  protecting 
and  aiding  humanity  in  thousands  of  other  direc- 
tions. It  is  this  insistence  on  complete  ultimate 
analysis  which  gives  to  chemistry  one  of  its  most 
powerful  resources — for  with  complete  knowledge 
comes  control,  in  the  form  of  wise  use  of  what  nature 
offers  and  also  in  the  opportunity  for  improving  on 
what  nature,  blindly,  has  furnished  to  man. 

r>i,      '  ^  A  simple  consideration  from  the 

r-       r  pomt  or  view  now  gamed  will  re- 
Goes  rar  ^     ,     ^  .        1       .     ,  . 
B        d  ih  ^            ^^^^       y  ^^^"^ic^l  investi- 
RZleof  the  ^^^^^^  ^^^  become  a  most  power- 
Microscope  in  ^"1    instrument    in    biological,    in 

D.  ,  ,     medical  research:  it  is  well  known 

Biology  ana        1        .      1  ,  .  ,  ,         ,. 

Medicine  ,       ^^  ^^^  P^^^  biology  and  medi- 

cine have  used  as  their  greatest  in- 
strument of  precision  the  microscope,  which  led  in- 
deed to  the  great  discoveries  of  the  cellular  struc- 
ture of  living  matter,  of  the  germ  theory  of  life — 
as  opposed  to  the  exploded  theory  of  spontaneous 
generation — of  the  germ  theory  of  diseases,  etc. 
But  the  microscope,  with  all  its  marvelous  improve- 
ments, can  go  no  farther  in  analysis  than  the  cell  and 
its  divisions — whereas  chemistry  can  and  does  go 
much  farther.  For  within  the  boundaries  of  even  a 
minute  cell,  there  are  dozens  of  different  principles, 
there  are  myriads  of  molecules,  which  defy  the 
power  of  the  finest  optical  instruments;  but  they  are 
subject  to  the  keen,  patient,  analytical  and  synthetic 
quest  of  the  chemist!     "There  is  a  constant  mo- 

[21] 


lecular  Interchange  between  the  cell  and  its  environ- 
ment." ''Cell-secretion,  cell-respiration  and  cell- 
nutrition  are  clearly  only  different  aspects  of  the 
same  whirl  of  molecular  activity."  (Haldane  of 
Oxford.)  In  a  word,  chemistry  is  now  called  upon 
to  provide  the  medical  investigator  with  the  most 
powerful  ultra-microscope  the  world  has  ever 
known,  to  lead  him  far  beyond  the  limits  of  his 
present  bounds  of  knowledge.  This  in  short  is  the 
reason  why  medicine  and  biology  in  general  have 
found  it  necessary  to  turn  to  chemistry  for  the  final 
solution  of  many  of  their  greatest  problems :  the  old 
methods  stop  at  the  limits  Imposed  by  the  micro- 
scope— with  the  invocation  of  the  aid  of  chemistry 
there  is  no  limit  to  ultimate  analysis,  down  to  the 
minutest  particles,  the  molecules  and  atoms.  In  turn, 
the  chemist  needs  in  this  service  the  advice,  indeed 
the  undivided  cooperative  effort  of  the  medical 
investigator,  the  pathologist,  bacteriologist.  Internist, 
for  only  such  cooperation  will  bring  the  vital  prob- 
lems of  medicine  home  to  the  consciousness  of  the 
experts  In  the  fundamental  science :  What  the  naval 
and  army  experts  meant  to  the  research  staff  of  the 
Chemical  Warfare  Service,  the  medical  leaders  must 
mean  in  this  proposed  cooperative  attack  on  disease 
with  the  aid  of  the  fundamental  sciences  of  life. 

Wh  tth  ^^  ^^^^   *^^   better  appreciate 

^,       .    ,  the  vital  possibilities  of  this  part- 

Cnemical  i  .       .r                     r 

M  th  d  nership,  if  we  turn  for  a  moment 

A  T  1,  J    from  the  consideration  of  chemls- 

Accomplished  ,  ,.  .  i  i 

with  D  ^^^  ^       medicine  to  observe  what 

a  complete  triumph  has  already 
been  brought  to  mankind  by  exactly  this  type  of 
chemical  Investigation  In  the  domain  of  dyes.  Origi- 
nally dyes  were  obtained  exclusively  from  natural 

[22] 


sources — indigo  and  alizarin  or  turkey-red  and  a 
few  others  from  plants,  carmine  and  some  others 
from  animal  sources.  Then,  in  1856  Sir  William 
Perkin  accidentally  prepared  the  first  aniline  dye 
mauve  (while  trying  to  make  quinine  artificially), 
and  after  that  chemists  from  time  to  time  stumbled 
similarly  on  other  even  more  valuable  dyes,  ma- 
genta, methylene  blue,  the  beautiful  rhodamines,  etc. 
Already  in  the  sixties,  pioneer  chemists  started  on  the 
finest  ultimate  analysis  of  the  dyes — determining  in 
fact  the  exact  way  in  which  the  atoms  in  the  smallest 
particles  of  each  dye  are  joined  together.  Graebe 
and  Liebermann  succeeded  in  doing  this  for  alizarin 
(turkey-red),  Baeyer  for  indigo,  Bernthsen  later 
for  methylene-blue,  and  others  for  a  number  of 
other  fundamental  dyes.  The  results  of  this  ex- 
ploration of  the  ultimate  minutiae  of  dyes  has  been 
^        J  the  complete  conquest  by  man  of 

r^  ^  the   domain   of  color  production: 

Conquest  i-        •  j 

,  ^  J  alizann      was      at      once      made 

of  Color  ^  .  ,  .       , 

D    J    *•  from  coal-tar  products  previously 

Production  ,    .  i      /-  1    •  1      •      j 

w^asted,  mstead  or  bemg  obtamed 

from  madder,  and  large  acreages  were  turned  from 
the  cultivation  of  madder  to  the  growth  of  wheat 
and  other  needed  crops.  Indigo  is  now  made  arti- 
ficially of  a  purity  greater  than  that  of  the  natural 
product  (because  free  from  admixed  rubbish  and 
foreign  dyes)  and  the  indigo  fields  are  giving  way 
to  food  crops — a  distinct  gain  to  man.  Even  more 
important  is  that  by  comparative  studies  of  the  struc- 
tures of  the  molecules  of  a  number  of  dyes,  the  key 
to  the  whole  mystery  of  color  production,  and  color 
quality  has  been  gained  by  man,  with  the  result  that 
we  can  now  produce  dyes  of  any  given  qualifications 
as  to  color,  shade,  stability  to  air,  to  light,  soap,  and 

[23] 


water,  sensitiveness  to  light  (for  photographic  pur- 
poses) indeed  even  of  two  colors  combined  in  a 
single  dye  (as  in  the  beautiful  fluorescent  shades  in 
silks).  This  complete  conquest  of  the  domain  of 
color  occupied  some  forty  years;  Is  it  surprising  that 
jjj  .  chemists  are  quietly  but  absolutely 

^  ^        confident,    with    the    aid    of    the 

Conquest  ,.,.'.  i      r     i      • 

,    ,  biological  sciences  and  or  physics, 

rh't  ^^    ^^    ultimate    conquest    in    the 

,  ,. . ,  domain  of  life  products,  of  medi- 

oi  Life  .       ,        .   .  1  .  ,  1 

cine  by  giving  to  biology  the  ser- 
vice of  these  same  methods  of  complete  ultimate 
analysis?  But  they  do  realize  that  where  a  little 
over  a  generation  sufficed  for  the  conquest  of  the 
domain  of  color  with  only  a  few  dozen  funda- 
mentally important  dyes,  life  with  its  thousands  of 
important  components  will  be  a  far  greater,  as  it  is 
a  vastly  more  important,  field  of  conquest,  requiring 
generations  of  Intensive  workers.  But  that  em- 
phasizes so  much  the  more  the  urgent  need  for  a 
concentrated,  multiple  attack — so  that  time  may  be 
saved  by  swifter  progress  year  after  year. 

III.     Constructive  Chemistry  in  the  Service  of 
Medicine 

After  this  preliminary  survey  of  the  aims  and  re- 
sources of  this  phase  of  chemistry,  let  us  ask  now 
without  further  delay,  w^hat  specific  services  construc- 
tive chemistry  can  and  must  render  to  medicine  in 
the  prevention  and  cure  of  disease.  We  find  that 
chemistry  from  its  constructive  side  can  be  of  great- 
est services  in  three  specific  lines  of  attack,  which 
are  arranged  not  in  the  order  of  fundamental  Im- 
portance but  rather  in  the  order  of  simplicity  of 

[24] 


attack    and   consequent    promise    of    comparatively 

earlier  success : 

,.         ,  I.  The     preparation     of     the 

Lines  of  .^  j  ..  r      ^u 

J       /  specific  medicament  tor  the  cure  or 

alleviation  of  the  specific  disease. 

2.  The  isolation,  study,  and,  if  need  be,  the  arti- 
ficial preparation  of  pure  organic  principles  of 
fundamental  importance  to  our  life,  such  as  princi- 
ples of  secretion  of  the  body  organs,  of  which  a 
deficiency  or  an  excess  would  cause  disease  (goiter, 
acromegaly,  dwarfism,  gigantism,  and  probably 
diabetes,  gout,  etc.). 

3.  The  complete  ultimate  analysis  of  the  constit- 
uents of  our  body  cells,  of  the  components  of  the 
blood,  of  tissues,  together  with  the  complete  ultimate 
analysis  of  the  components  of  our  foods — so  that 
we  may  have  complete  knowledge  of  the  body  in 
health  and  of  what  it  needs  to  preserve  its  health. 

The  Specific       ^  Taking  up  first  the  problem  of 

,,  J.  ^      the  specinc  medicament  tor  specinc 

Medicament  ^  r    i    1        •  1 

purposes,  we  nnd  chemists  engaged 

in  two  lines  of  efi[orts:  in  the  first,  they  start  from 
natural  remedies  already  known,  examine  them  ex- 
haustively and  with  the  knowledge  gained  improve 
on  the  natural  product;  In  the  second  line  of  effort, 
they  start  out  independently  of  natural  drugs  and 
attempt  to  prepare  the  specific  remedy  for  the  de- 
struction of  the  specific  invading  germ,  or  the  specific 
remedy  for  some  faulty  adjustment  of  the  human 
organism  In  disease. 

A  brief  survey  of  the  results  obtained  from  the 
study  of  the  drug  cocaine  will  illustrate  sufficiently 
the  value  of  the  effort  to  improve  on  natural  remedies. 
Cocaine  Is  a  white,  crystalline  substance,  like  salt  of 
sugar,  which  brought  in  dilute  solution  (4  per  cent) 

[25] 


on  the  tongue,  under  the  eyehd,  or  Injected  under 
the  skin,  was  found  by  Von  Anrep  to  suppress 
locally  all  sensation  of  pain.     It  was  first  used  in 

The  Story        t^T'^     Xr  *'     ^Pthalniologist 
,^      .  Koller,   or   Vienna    (now  of  New 

oi  Cocaine        xr     i  \  i  11  -        1 

audits  lork),  and  proved  to  be  an  inval- 

p       .  uable  aid  to  surgery  for  the  pro- 

duction of  local  anaesthesia,  making 
possible  painless  operations  without  recourse  to 
general  anaesthesia  under  ether,  chloroform  or 
laughing  gas.  But  cocaine  had  three  grave  defects: 
one,  its  rareness  and  resultant  expensiveness,  which 
limited  its  usefulness,  the  other  more  serious  defects 
that  it  is  difficult  to  sterilize,  and  especially  that  it 
is  decidedly  poisonous  and  occasionally  In  minor 
operations — In  those  of  dentistry,  for  Instance — 
fatal  results  ensued  not  warranted  by  the  conditions. 
Cocaine  then  fell  under  the  searching  scrutiny  of 
chemists,  who  subjected  it  to  ultimate  analysis  for 
the  determination  of  the  structure  or  the  arrange- 
ment of  the  atoms  in  the  smallest  particle,  the  mole- 
cule of  cocaine;  there  are  no  less  than  43  atoms  In 
this  molecule,  arranged  in  a  peculiarly  complex, 
labyrlnthal    fashion^    and   It   took   three    successive 

^The  structure  of  cocaine  is  indicated  by: 


Only  the  parts  surrounded  by  dotted  lines  are  of  value  in  pro- 
ducing local  anaesthesia. 

[26] 


attacks  by  leading  chemists  to  reach  a  final  solution 
of  the  problem.  With  this  vantage  gained  at  how- 
ever great  a  cost  of  mind  and  labor,  the  problem  of 
local  anaesthesia  immediately  made  tremendous 
progress.  It  was  found  that  only  part  of  the  mole- 
cule has  the  beneficent  anaesthetic  effects  of  cocaine, 
while  another  part  is  closely  related  to  the  deadly 
principle  of  hemlocks,  coniine,  famous  as  the  poison 
Socrates  was  forced  to  take,  and  a  third  part  is  re- 
lated to  nicotine.  And  now  the  chemist  was  in  a 
J  .  position  to  improve  on  nature  and 

T.J  invent  local   anaesthetics   with   the 

on  Nature  .  ^  .  •  j      -^u      ^  v 

virtues  of  cocaine  and  without  its 

excessive  toxicity — exactly  as  a  conscientious  mod- 
ern architect  in  planning  a  house  would  insure  the 
absence  of  noxious  rooms  deficient  in  air,  light,  heat 
or  drainage.  We  have  now,  in  fact,  a  number  of 
those  artificial  local  anaesthetics — procaine  (intro- 
duced as  novocaine),  beta-eucaine,  apothesine,  etc., 
and,  more  recent,  benzyl  alcohol  and  related  prod- 
ucts— better  than  cocaine,  because  less  poisonous. 
The  extent  to  which  they  are  being  used  in  surgery 
is  growing  very  rapidly  and  they  hold  out  to  man 
the  possibility  of  some  of  the  greatest  advances  of 
the  future  in  this  field;  even  major  operations,  for 
appendicitis,  hernia,  uterine  troubles,  are  being  per- 
formed now  under  local  anaesthesia,  and  it  is  to  be 
hoped  that  the  field  of  general  anaesthesia,  with  its 
grave  fundamental  principle  of  poisoning  the  whole 
system  with  ether,  chloroform  or  laughing  gas,  will 
grow  more  and  more  limited  to  unusually  prolonged 
or  unusually  painful  operations.  We  have  here, 
then,  a  first  real  triumph  in  medicine  of  the  science 
that  triumphed  so  completely  in  the  field  of  dyes. 

[27] 


In  Itself,  this  successful  effort  has  been  an  untold 
blessing  to  thousands  of  sufferers,  but  the  great  les- 
son the  story  of  the  conquest  of  local  anaesthesia 
teaches  Is  that  it  Is  a  golden  promise  of  ultimate  vic- 
tory heartening  the  army  of  chemists  in  their  grim 
onslaught  on  the  more  profound  and  vast  problems 
of  the  chemistry  of  all  life. 

Chemistry  Another   rather   recent,    and   in 

Q       .  many  respects  a  most  important  in- 

I  ^  e  stance  of  this  kind,  Is  the  specific 
Lenrosv  remedy  used  with  much  success  In 
the  treatment  of  leprosy:  chaul- 
moogra  oil  Is  an  Irritating,  nauseating  natural  prod- 
uct, used  for  perhaps  sixty  years  In  India  In  the  treat- 
ment of  leprosy.  Even  in  those  days  of  uncertain 
quality  and  uncertain  method  of  administration,  the 
oil  proved  Its  usefulness,  but  a  positive  and  most 
signal  advance  In  the  successful  treatment  of  the  dis- 
ease was  made  only  through  the  Isolation  by  chem- 
istry from  the  nauseating  natural  product  of  clean, 
pure  acids  which  were  combined  with  ethyl  alcohol 
and  thus  formed  a  new  drug  which  could  be  used 
hypodermlcally.  In  a  recent  publication,  78  cases 
of  apparent  cure  by  this  Improved  drug  have  been 
reported.  While  even  greater  Improvement  In  the 
medicament  is  looked  for  by  further  painstaking  re- 
search, we  have  already  an  effective  remedy  for  one 
of  the  most  hopeless  of  diseases — a  result  of  the 
active  cooperation  of  medicine  and  chemistry. 

Some  Other  Improvements  of  other  natural 

Improved        ^^^^^  have  similarly  been  accom- 

Drues  pHshed.      A    few    Instances    must 

suffice  here.     Atropine,  as  used  by 

the  oculist,  puts  the  eyes  out  of  commission  for  two 

I28J 


or  three  days — the  chemist  has  supplied  homatropine 
for  the  busy  man,  reducing  the  effect  to  two  or  three 
hours.  Morphine,  the  Dr.  Jeykll  and  Mr.  Hyde 
of  nature's  store  of  remedies,  with  its  blessed  alle- 
viation of  pain,  carries  the  curse  of  the  habit-forming 
drug.  Chemistry  found  with  morphine  the  drug 
codeine,  also  in  opium,  whose  effects  resemble  those 
of  morphine  except  that  it  is  very  much  less  likely 
to  produce  habit.  There  is  little  codeine  in  opium, 
but  again  chemistry  easily  converts  morphine  into 
codeine,  giving  mankind  an  ample  supply  of  the 
blessed  sedative  shorn  of  its  curse.  Morphine  is 
similarly  readily  transformed  into  ethylmorphine 
(dionlne),  which  resembles  codeine  in  its  action  and 
which  has  also  found  important  applications  in  the 
treatment  of  certain  diseases  of  the  eye. 

^,       .  In  1886  the  pharmacologist,  W. 

.. , .  Von  Schroeder,  first  studied  by  ex- 

Aid  m  ,  ,  -  -If 

n-      ^.  perimental   work   on   animals   the 

diuretic  action  of  caffein  and  at- 
tempted to  explain  why  this  drug  was  uncertain 
and  not  always  reliable  as  a  diuretic.  Chemists 
had,  however,  found  another  principle,  theobromin, 
very  closely  related  to  caffein  in  molecular  struc- 
ture and  composition.  What  was  more  natural 
for  the  experimental  pharmacologist  than  to  try 
the  effects  of  this  close  relative  of  caffein  to  which 
chemical  study  had  pointed?  And,  in  fact,  theobro- 
min was  found  far  more  useful  and  dependable  than 
caffein  in  its  diuretic  action  and  has  largely  replaced 
it.  Still  a  third  related  compound,  theophyllin,  was 
discovered  by  chemists  and  found  the  best  of  all. 
The  natural  supply  of  these  dr«gs  being  rather 
limited,  chemists  solved  In  short  shrift  the  task  of 
preparing  them  artificially  in  any  quantity,  desired. 

[29] 


^,       .  ^     n/r  Profound  study  of  other  natural 

Lnemistry  May  ,.  i       i  n  i     •  i 

TT  1    /  medicaments  should  be  pursued  with 

tielp  Lure  .  .         ,         .  ^ 

D  .         great  intensity;  there  IS  every  reason 

fneumonia  ,    ,.  ,  i-r       .  r 

to  believe  thatamodincation  or  qui- 
nine can  ultimately  be  prepared  which  will  be  a  spe- 
cific cure  of  pneumonia.  One  modification,  optochin 
( ethyl  hydrocupreine )  is  already  known  to  be  a  specific 
in  killing  pneumococcus  germs  in  glass  vessels  {in 
vitro)  and  is  used  successfully  in  external  pneumo- 
coccus infections,  as  of  the  eye,  but  it  is  still  too 
poisonous  to  be  used  in  sufficient  strength  in  the 
blood  to  combat  the  hosts  of  invading  germs  in 
pneumonia  itself.  No  greater  blessing  could  be 
granted  mankind  than  the  discovery  of  such  a  spe- 
cific, as  pneumonia  is  one  of  the  two  diseases  re- 
sponsible for  the  greatest  loss  of  life  in  the  world 
(tuberculosis  is  the  other  one).  The  tragedy  of  the 
situation  is  the  tremendous  waste  of  life,  for  instance 
during  the  recent  influenza  epidemics,  while  the 
preparation  of  such  a  specific  is  being  looked  for. 

c       rr-  No  matter  how   ardently,   how 

bave  lime  i  .,r  n       i  i    •    i    •  i 

^Ij  1  skiliully,  the  work  is  being  pursued, 

the  lesson  of  the  past  teaches  us 
that  only  by  a  massive  coordinated  attack  of  many 
workers  can  we  hope  to  save  time  and  all  it  means 
to  us.  A  generation  ago  one  of  the  greatest  spe- 
cialists in  children's  diseases  in  New  York  City  lost 
his  only  son  through  diphtheria.  It  was  a  heart- 
breaking tragedy  for  him  that  science  had  not 
brought  diphtheria  antitoxin  into  the  world  just  a 
few  years  earlier,  so  that  he  might  have  saved  his 
own  son.  In  how  many  thousands  of  homes  is  this 
tragedy  being  reenacted  today  in  the  face  of  dis- 
eases which  man  ultimately  must  and  will  conquer. 
Chemists,  as  stated  above,  are  also  attacking  the 
[30] 


problem  of  the  specific  remedy  for  the  specific  disease 

quite  independently  of  any  compounds  that  nature 

y,    ^  .     has  suppHed.  The  greatest  instance 

J      fc  •        ^^     ^^^^     ^^^^     ^^     arsphenamine 

Tl^  c      '£         ("606'*    or    salvarson),    prepared 
the  bpecijic       ,       t^i    ,-  •  1  1        r 

i  S  hil'  y^  Jbhrhch  as  the  result  or  a  sys- 
tematic  effort  to  prepare  a  drug 
that  would  kill  the  invading  germs,  the  spirochetes 
of  syphilis,  without  injury  to  the  patient.  It  is  again 
to  be  noted  that  this  first  great  successful  attack  on 
a  most  widespread  disease  was  brought  to  a  success- 
ful issue  by  the  closest  cooperation  between  chem- 
istry and  medicine.  Dr.  Ehrlich,  from  his  earliest 
years  in  medical  investigation  (1884)  was  charac- 
terized indeed  by  the  application  of  chemistry  to  his 
problems.  His  first  research  work  was  on  dyes  used 
as  stains,  a  chemical  problem.  The  very  name  "606" 
indicates  how  he  gradually  accomplished  his  purpose 
— using  first  one  substance  of  a  definite  known  molec- 
ular structure,  then  another,  until  seeing  improve- 
ment ahead,  he  modified  first  this  and  then  that  part 
of  the  structure  of  his  molecules  until  finally  complete 
success  was  accomplished  after  605  imperfect  re- 
sults, exactly  as  the  sculptor  models  from  his  coarse 
clay  the  perfect  head  through  a  long  series  of  in- 
complete, imperfect  stages.  The  tremendous  value 
to  mankind  of  this  brilliant  chemo-medical  triumph 
is  realized  when  we  recall,  first,  that  "606^'  and 
later  developed  drugs  of  the  same  kind  properly  used 
are  specific  cures  for  the  disease  syphilis,  and,  second, 
that  this  disease  is  so  widespread  that  it  has  been 
estimated  that  in  the  United  States  alone  we  have 
over  ten  million  cases  of  the  disease  in  its  various 
stages  and  dread  sequels. 

[31] 


.  ^,       .    ,  Another  notable  instance  of  the 

A  Lnemical  -r  •  i      i        •     i  i      • 

c      ,     .  artincial   chemical    remedy   is   cin- 
byntnetic  to         .  ,.  .        ,  ■'       .       . 

J.  J.        c     t  ^^^P^^    (introduced   as  atophan), 

the  uric  acid  ellmlnant,  an  allevla- 

tlve,  and  in  some  cases  a  preventive,  in  gout. 

In  the  field  of  hypnotics,  used  to  produce  sleep 
and  allay  nervous  excitement  (insomnia,  epilepsy, 
etc.),  constructive  chemistry   has  advanced  far  Its 

^  .        ,     campaign    toward    complete    con- 

^  quest.   The  advance  has  been  made 

Conquest  7  i  ^•  i  •  i 

•     c  J  *•  from  the  earlier  and  sometimes  dan- 

gerous  hypnotics,  chloral  and  its 
derivatives  (great  blessings  In  their  day  but  danger- 
ous because  highly  toxic,  like  chloroform),  from  the 
hablt-forming  sulphonals  and  trionals,  to  such  hyp- 
notics as  barbital  (introduced  as  veronal),  luminal 
and  adalln,  which  are  very  closely  related  to  products 
formed  naturally  in  the  body,  and  produce  sleep  with 
a  minimum  of  disturbance  and  risk  to  the  system. 
Luminal  is  claimed  to  be  a  specific  to  relieve,  indeed 

A  Ch  'I  ^^  prevent,  the  seizures  of  epilepsy. 
;^      .J.  The  Importance  of  this  Invention 

.     ^  .,  of  modern  chemistry  was  revealed 

during  the  war  years  when  exhaus- 
tion of  our  supplies  of  the  drug  brought  in  its  wake 
pathetic  and  fruitless  appeals  from  nerve  specialists, 
hospitals,  patients  and  parents. 

„    ,  Another  disease  for  which  a  spe- 

Hookworm  t       1        •     1  1        1  r        j 

^      J  ,  cihc  chemical  cure  has  been  round 

^,       .    ,         is  that  caused  by  the  hookworm, 
Litiejnicals  n      >  1        i      1       •n* 

aitecting  over  a  hundred  miuions 

throughout  the  world  and  widespread  In  our  own 

Southern  States.     It  is  one  of  the  most  debilitating 

of  diseases.     The  chemical  thymol  In   conjunction 

with  chenopodlum  has  been  found  to  be  a  very  effec- 

[32] 


tive  agent  In  the  cure  of  hookworm,  but  again  it  is 
confidently  expected  that  some  modification  of  thy- 
mol could  be  elaborated  by  synthetic  chemistry 
which  would  be  even  more  efficient,  and  would  lead 
ultimately  to  the  complete  elimination  of  this  disease 
from  our  country. 

There  is  a  tremendous,  practi- 

ree    courges    ^^j,    undeveloped  field  for  greater 

Lack  bpecincs  i       r  'c  ^ 

^     '        work     here — specifics     are     most 

needed  now   for  tuberculosis   and  pneumonia,   and 

perhaps  even  for  cancer,  to  which  a  large  proportion 

of  mankind  falls  a  victim. 

^     ,  ,  In  any  efforts  in  this  direction, 

^  ..         .  we  must  always  remember  that  the 

Cooperation  •       r  i  j 

greatest  promise  for  success  would 

be  found  only  in  closest  cooperation  of  chemists, 
pharmacologists  and  medical  men.  The  past  is 
replete  with  impressive  lessons  emphasizing  the 
importance  of  such  cooperation.  Two  or  three  in- 
stances must  suffice  to  show  how  Important  this  les- 
son of  the  past  is.  Five  centuries  elapsed  between 
the  discovery  of  ether  by  chemists  and  Its  application 
TV  edlp  ^^^  surgical    anaesthesia,    five    cen- 

c  AT    .  turies  of  needless  suffering.     The 

first  chemical  used  to  produce  sleep, 
chloral  hydrate,  was  known  to  chemists  for  almost 
forty  years  before  the  pharmacologist  Llebreich  dis- 
covered that  it  produced  in  pain-racked  bodies  a 
peaceful  sleep  from  which  after  a  few  hours  the 
patient  awoke  greatly  refreshed.  Many  other 
hypnotics  and  sedatives  were  then  soon  found  among 
compounds  long  known  to  chemists. 

All  of  Ehrlich's  great  work  on  the  cure  of  syphilis 
was  accomplished  when  he  was  between  54  and  61 
years  of  age,  but  following  lines  of  thought  which 

[33] 


had  been  in  his  mind  for  30  to  35  years;  he  had  been 
waiting  all  that  time  to  get  the  full  cooperation  of 
chemists,  and  this  became  possible  only  through  the 
munificence  of  Frau  Speyer  in  Frankfort.  More  was 
then  accomplished  in  four  years  by  chemo-medkal 
research  than  in  four  centuries  of  medical  effort, 
including  hygiene  and  education. 

.     „    ,  Amyl  nitrite  was  discovered  by 

.        ,        a  French  chemist  in   1844,  but  it 
^  was    not   until    1867    that   it   was 

found  to  give  relief  from  the  agonizing  pains  of 
angina  pectoris.  Dr.  Brunton,  led  by  the  results  of 
experiments  of  the  pharmacologist  and  biochemist 
Gamgee,  made  this  discovery  and  thus  describes  the 
first  case  in  which  the  remedy  was  used  by  him: 
"There  was  one  poor  man  in  the  wards  suffering 
dreadfully  from  angina  pectoris;  he  used  to  have 
an  attack  every  night  and  for  two  hours  the  unfor- 
tunate man  would  sit  on  the  edge  of  his  bed  and 
could  not  move  forward,  backward,  or  to  one  side, 
with  his  face  pale  and  sweat  pouring  off  it,  in  per- 
fect agony.  The  administration  of  amyl  nitrite 
gave  him  instant  and  complete  relief."  There  are 
tens  of  thousands  of  persons  in  the  United  States 
alone  afflicted  with  this  dread  disease  of  the  heart,  to 
whom  amyl  nitrite  is  a  blessing  indeed.  These  tragic 
delays  resulted  from  the  wide  gap  that  existed  be- 
tween the  scientific  activities  of  investigators  in  medi- 
cine and  in  chemistry;  they  must  in  future  be 
prevented  by  Intensive,  closest  cooperative  effort  and 
interest. 

^,     nil  There    are    hundreds    of    thou- 

i  he  rroblem  a         r        rr  r  •    r  i 

,  rj    *     •  sands    or    sufferers    rrom    pamrul, 
0/  Hastening  .  ,.  ^  1  •  1      1 

n  J'  1  consummg  diseases  for  which  the 
£\.ei>iej  .  .        I       .    .       «  > 

remedy  awaits  the  joint  intensive 

[34] 


efforts  of  chemist,   pharmacologist   and  physician. 

How  many  years  must  they  wait?     That   is   our 

problem. 

p  The  second  great  field  of  effort 

p  .     .  ,        .     for  the  constructive  chemist  is  the 

c.         •  isolation,  study,  and  if  need  be,  the 

becretion  .  •'.  •     •    i  r 

preparation  of  pure  principles  or 

our  organs  of  secretion  and  of  other  principles  of 
vital  importance  to  healthy  life.  One  or  two  specific 
accomplishments  will  illustrate  the  vital  importance 
of  this  work.  After  Schafer  and  Oliver,  Szymono- 
wicz  and  Cybulski  had  noted  the  presence  of  a  vaso- 
constrictor principle  in  the  suprarenal  glands,  small 
glands  situated  just  above  the  kidneys,  Professor 
Th    S*         /     Abel,  of  Johns  Hopkins  University, 

E,  .       I   •         succeeded    in    isolating    this    prin- 
Lpinephnne        .   ,  .        ,    .         .     ,         i-    \      • 

ciple,   epinephrine    (adrenalin),   in 

the  form  of  a  derivative  and  prepared  a  number  of 
salts  of  this  derivative.  Later  J.  Takamine  precipi- 
tated the  pure  principle  itself  by  means  of  ammonia, 
a  precipitating  agent  which  Professor  Abel  had  al- 
ready used  in  this  work,  as  the  native  compound  in 
the  form  of  minute  crystals.  Its  chemical  structure 
was  later  determined,  with  the  result  that  epinephrine 
can  now  be  prepared  artificially.  The  manufacturer's 
patents  having  expired  (in  February,  1921),  the 
world  is  the  richer  for  wide  sources  of  manufacture 
of  this  invaluable  drug.  Some  of  the  very  great  ad- 
vantages of  the  isolation  of  this  pure  principle  are 
these:  It  is  injected  with  local  anaesthetics  (pro- 
caine, etc.),  causing  constriction  of  the  blood  vessels 
and  preventing  a  rapid  local  loss  of  the  anaesthetic, 
thus  reducing  the  amount  needed  very  materially  and 
reducing  correspondingly  the  danger  of  toxic  effects. 
Injected  hypodermically,  epinephrine  allays  within 

[35] 


a  few  minutes  the  spasms  of  acute  bronchial  asthma, 
an  untold  blessing  which  those  can  only  realize  who 
have  in  the  past  witnessed  helplessly  the  acute  suffer- 
ings of  a  patient.  Epinephrine  may  also  be  used  for 
the  quick  arrest  of  hemorrhage  of  a  capillary  or 
small  arterial  character — all  blessings  for  man. 

p  .       ,   .  Very  recently  (unpublished  work 

Epvnephrrne  ^^  ^^   ^         ^^  ^^^  York  City) 

bustams  the  .  ,  .  r     U 

jr        .  perhaps  the  most  miportant  of  all 

r,        s.'     n         uses  of  epinephrine  has  been  dis- 
(Jperative  Loses  t      i  •    •    t         i 

covered:  this  is  based  on  its  action 

on  the  heart.     Injected  In  such  a  way  as  to  provide 

for   very   slow    and   gradual    absorption,    it   Is    of 

extraordinary  value  when  used  in  preparing  old  or 

weakened   patients   for   operations,    fortifying   the 

heart  against  the  danger  of  shock  and  failure. 

rr  1.  '  Of  equally  great  value  is  the  in- 

Lpinephrine      .       .       ^  ^     ■',  ^    .    .       .       .  . 

D  .      jection  or  epinephrine  in  this  man- 

in  rneumonia     •'       .       ,        ^       ^  - 

ner  in  the  treatment  of  pneumonia. 

Used  from  the  earliest  stages,  it  reduces  the  danger 
of  death  from  heart  failure  to  such  an  extent  that 
eminent  physicians  with  its  aid  feel  safe  in  depend- 
ing on  the  normal  resistance  of  the  body  to  effect  a 
cure  of  this  dangerous  disease,  thus  avoiding  the 
dangers  of  antitoxin  injections.  These  discoveries 
of  today  emphasize  the  vital  Importance  of  exhaus- 
.  tlve  investigation  by  the  joint  efforts  of  chemist, 
pharmacologist  and  physician. 

rjnj^        .    ,  More  recently  Dr.  E.  C.  Ken- 

r^i      -7        dall,  of  the  Mayo  Foundation,  has 
C      ucst        isolated    thyroxin,    the    crystalline 
active    principle    of    the    thyroid 
gland,  which  regulates  the  metabolism  (the  combus- 
tion of  our  food)   of  the  body.     This  principle  is 
so  tremendously  active  that  an  occasional  dose  of 

[36] 


a  fraction  of  a  milligram  (a  minute  fraction  of 
a  grain)  is  able  to  cure  cretinism,  a  condition  of 
stunted  growth  of  body  and  mind,  and  myxedema,  a 
similar  condition  developing  in  adults.  The  arti- 
ficial preparation  of  thyroxin  is  only  a  question  of 
time  and  effort  and  one  more  outpost  of  the  bulwarks 
of  life  will  thus  have  been  conquered  by  the  chemist. 

n    i_f        V  There  are  many  other  vital  se- 

Problems  Yet  .  i      •     i     •  r     i 

rr         I    J       cretions  the  isolation  or  whose  pure 
Untouched  •     .   ,  i  if 

principles     must     be     undertaken: 

the  isolation  of  the  active  principle  of  the  pituitary 
glands,  controlling  of  normal  growth,  the  Isolation 
of  further  active  principles  of  digestion  and  metab- 
olism (for  the  cure  of  gout,  diabetes  and  other 
metabolic  diseases),  the  Isolation  of  the  active  hor- 
mone controlling  normal  sex  functions,  are  a  few  of 
the  great  problems  lying  almost  untouched  for  lack 
of  workers  in  the  field  of  chemical  effort  In  the  ser- 
vice of  medicine. 

p  Another  great  line  of  effort  In 

D  .     .  ,        ,     this   direction    should   be   the    at- 
rrincipLes  of  •     i  i  •     •   i 

A  tit  tempt  to  isolate  the  pure  principles 

of  antitoxins,  bacterial  vaccines, 
and  serums  now  used  so  widely  In  the  cure  or  pre- 
vention of  Infectious  diseases  (diphtheria,  tetanus, 
streptococcus  Infection,  meningitis,  etc.).  The 
fluids  which  are  now  injected  contain,  no  doubt,  only 
very  small  quantities  of  the  pure,  active  principles, 
mixed  w^Ith  a  vast  proportion  of  Inert  and  In  part 
harmful  matter  (horse  serum,  etc.).  Every  physi- 
cian of  standing  has  rejoiced  to  have  been  delivered 
from  the  old  days  when,  to  secure  the  effect  of 
strychnine,  he  was  compelled  to  prescribe  tincture  of 
nux  vomica  of  an  Indefinite  composition,  when  to  pro- 
duce the  effect  of  quinine  he  had  to  prescribe  ground 

[371 


cinchona  bark,  etc.,  etc.     Chemists  isolated  strych- 
nine, quinine,  morphine,  atropine,  cocaine,  hyoscya- 
min,  pure  principles  from  the  crude  drugs  offered  by 
.  ,      ^  nature,   with   the    tremendous   ad- 

f  p  vantages,  hrst,  or  quantitative  ac- 

p  .     .J  curacy  in  administration  replacing 

an  approximate  and  sometimes  dis- 
astrous guess,  and  second,  of  putting  into  the  hands 
of  physicians  the  possibilities  of  almost  instantaneous 
effects  by  hypodermic  injections  of  pure  solutions 
of  the  pure  principles.  In  the  course  of  time  it  must 
be  chemists  again  who  will  place  in  the  hands  of  the 
physician  the  pure  active  principles  of  the  antitoxins, 
vaccines  and  serum  mixtures,  which  are  the  real 
curative  principles  and  whose  action  must  at  best 
be  handicapped  by  the  presence  of  a  preponderance 
of  useless  impurities  injected  into  our  veins  and  tis- 
sues. The  isolation  of  such  specifics  should  be  fol- 
lowed by  the  exhaustive  minute  study  of  structure, 
revealing  the  why  and  wherefore  of  action,  opening 
up  the  way  possibly  to  refinement  and  improvement. 
^     ^  How  immediately  urgent  intensive 

K^Ul     \jri6ut6Sv  I  /*1*1*1  1  'J 

jyr     ,  work  or  this  kind  must  be  consid- 

ered is  brought  home  to  us  by  the 
heartrending  helplessness  of  physicians  in  the  pres- 
ence of  certain  sudden  diseases  when  patients  full 
of  strength  and  vitality  and  otherwise  healthy,  never- 
theless face  extinction  because  of  the  inability  of  the 
ablest  of  physicians  to  reach  the  source  of  destruc- 
tion. The  treatment  of  pneumonia  by  antipneumo- 
coccus  serums  holds  out  great  promise  of  successful 
combatting  of  one  of  our  greatest  scourges  in  at 
least  a  fair  proportion  of  the  cases.  But  it  is  well 
understood  among  physicians  that  the  injection  of 
large  quantities  of  serums  in  such  treatment  may  be 

[38] 


attended  by  new  and  serious  dangers  of  anaphylactic 
shock  and  other  complications.  These  difficulties 
without  doubt  would  be  decidedly  lessened  if  chem- 
ists succeeded  in  separating  from  serums  the  minute 
amount  of  pure,  active  principle  which  must  be 
present.  This  problem,  with  others  of  the  same 
character,  is  perhaps  the  very  greatest  immediate 
problem  awaiting  the  attack  of  chemo-medical  re- 
search— and  scarcely  a  start  has  yet  been  made 
toward  the  goal  I 

c  J       j'^'  Endocarditis,  an  infection  of  the 

Endocarditis  a         .  r    i      i  •  i         i- 

„  ,  ,      rri        1    valves  or  the  heart,  is  another  dis- 
Helpless  1  ragedy  ,     .  i  •  i  i-  •  j 

ease  berore  which  medicine  stands 

practically  helpless,  although  the  victim  may  be  a 
young  man  or  young  woman  in  the  bloom  of  life  and 
otherwise  in  brilliant  health !  It  is  scoring  Its  trage- 
dies among  rich  and  poor,  the  well-protected  and  the 
most  exposed,  by  the  thousand  each  year.  Antitoxins, 
auto-vaccines,  serums,  are  used  but  are  of  little  avail, 
although  it  Is  known  from  laboratory  experiments 
that  in  sufficient  doses  they  should  kill  the  Invading 
germ.  Again,  it  Is  most  likely  the  huge  quantity  of 
useless  impurities,  such  as  horse  serum,  which  limits 
the  physician  in  the  application  of  these  remedies. 
Might  not  relief  be  found  In  the  swift,  sure  action 
of  the  pure,  active  principle,  to  which  the  germ  Is 
sensitive,  injected  intravenously  in  measured 
strength,  bereft  of  Its  present  load  of  Ineffective  Im- 
purities, before  the  germ  has  Itself  become  immune 
to  the  principle  ?  In  the  present  state  of  tragic  help- 
Health  and  ^^^sness,  the  effort  certainly  would 
F  od  ^^  worth  making. 

The  third  great  field  of  effort  in 
behalf  of  medical  science  by  constructive  chemistry 
is  found  in  the  exhaustive  study  of  all  the  important 

[39] 


components  of  the  cell  contents  and  tissues  and  fluids 
of  the  body  carried  out  parallel  with  a  similar  exhaus- 
tive study  of  our  food  resources.  The  Martian  archi- 
tects studying  the  structures  of  New  York  City  in  the 
way  suggested  above,  must  need  examine  and  under- 
stand every  part,  large  or  small,  entering  into  the 
edifices  of  the  highly  complex  community  if  they 
would  undertake  to  keep  the  city  in  first  class  repair 
and  working  order  under  the  stress  of  the  tremendous 
wear  and  tear  of  the  life  flowing  through  its  veins. 
Thus,  they  would  insure  that  into  the  city  are 
brought  all  of  the  myriad  parts,  or  the  materials  for 
their  manufacture,  needed  for  replacement  and  re- 
pair, ranging  from  obvious  rail,  brick,  stone,  terra- 
cotta, tile,  beam,  to  the  hidden  finest  bolts  and  screws, 
levers  and  wheels  of  the  controlling  devices  of  eleva- 
tors, of  lighting,  water,  plumbing,  drainage  systems. 
^,       .  In    the    same    way,    the    body 

AT  T?  J  demands  an  impressive  variety  of 
p     -I    f  materials  tor  its  healthy  sustenance. 

In  its  blind  effort  to  contribute  these, 
a  part  of  humanity  has  been  inclined  to  overeat,  with 
Its  resultant  ills  of  functional  disturbances.  Another 
large  proportion  of  humanity  has  been  well  nour- 
ished in  quantity  but  undernourished  In  regard  to 
particular  units  of  sustenance — with  the  resultant 
diseases  of  nourishment,  berl-beri,  pellagra,  rickets, 
etc.  Much  work  has  already  been  done  by  the  chem- 
ist In  the  exhaustive  analysis  of  food  products,  such 
as  carbohydrates,  fats,  amino-acids,  but  only  a  be- 
ginning, however  Important,  has  been  made,  and 
every  result  demonstrates  more  convincingly  the 
need  of  a  much  more  complete  knowledge. 

The  fundamental  work  of  the  chemist,  Emil 
Fischer,  on  the  structure  and  chemistry  of  the  sugars 

[40] 


opened  the  gates  for  all  the  more  recent  work  on 
carbohydrate  metabolism  and  its  pathologic  varia- 
tions as  found  in  diabetes.  Again  Fischer's  work  on 
the  amino-acids,  a  purely  chemical  study,  forms  the 

r.     J            f  very    foundation    of    all    modern 

Fundamental  \                   ^  .            ^  v    i- 

^i       .    1  o    J  work  on   protem   metabolism,    on 

Chemical  btuay  .     r    ^    .      .           tttvi    ^i        •  j 

•^  protem  functionmg.     With  the  aid 

of  the  pioneer  work  of  this  chemist,  recent  work  has 

shown  that  while  the  human  body  can  construct  a 

considerable  number  of  its  needs  from  the  common 

ingredients  of  all  foods,  there  are  other  vital,  specific 

needs  which  must  be  supplied  to  it  in  finished  form 

or  else  starvation  of  vital  parts  and  disease   and 

death  follow  in  the  midst  of  what  otherwise  would 

be  plenty.    It  will  be  the  duty  of  chemists  to  furnish 

a  complete  statement  of  such  specific  needs,  to  show 

just  how  they  can  be  satisfied,  to  help  out  perhaps, 

indeeil,  by  showing  how  certain  rare  and  difficult 

units  can  be  manufactured  artificially. 

c        n       ^         Indeed,      cooperation     between 
some  Kecent  j-  •  i    i        •         i         t        i 

y.       .  medicine  and  chemistry  has  already 

scored  important  victories  in  this 

field:    Diseases  such  as  scurvy  and  beri-beri  have 

been  found  by  physicians  and  chemists  to  have  their 

source   in  the   lack   of   certain   minute   but  vitally 

important     principles — hence     called     vitamines — 

found  in  some  but  not  in  all  foods,  and  with  these 

Scurvy  Cuted     discoveries  and  the  results  of  the 

^^^  analysis  or  a  great  variety  of  foods 

PrLented        P^^perly    brought    home    to    the 

practitioner  the  world  over,  these 

diseases  should  vanish  from  the  face  of  the  earth. 

Again,  in  the  thyroid  gland  minute  quantities  of  the 

chemical  element  iodine  are  found.     Its  absence  in 

the  diet  is  likely  to  cause  thyroid  trouble  such  as 

[41] 


goiter.  The  observation  that  goiter  is  very  prev- 
alent around  the  Great  Lakes,  especially  in  young 
girls  and  young  women,  led  to  an  attempt  to  pre- 

P  .  vent  the  development  of  goiter  in  a 

Att  ked  town  in  Ohio  by  the  giving  of 
small  quantities  of  sodium  iodide 
to  the  school-girls  for  short  periods.  The  results 
under  competent  medical  direction  have  been  as- 
tonishingly good,  and  there  is  no  question  but  that 
this  simple  instance  of  cooperation  between  chem- 
istry and  medicine  will  lead  to  the  prevention  of 
many  thousands  of  cases  of  disease  with  its  atten- 
dant dangers  and  unhappiness! 

-,        ,  That  the  possibility  exists  that 

„    ,,  certain   mental   disorders   may  be 

Froblems  ,        ,     .  .        .     ,         •     •   t 

produced    by    chemical    principles 

taken  in  with  our  food  or  by  toxic  principles  pro- 
duced from  our  food  under  abnormal  conditions  is 
shown  by  the  fact  that  certain  chemicals  are  well 
known  to  affect  the  mind :  In  Beverly's  History  of 
Virginia  in  which  Bacon's  Rebellion  is  described,  a 
striking  instance  of  the  kind  is  found,  where  a  com- 
pany of  soldiers  partaking  of  a  certain  herb  (Datura 
Stramonium,  containing  the  principle  hyoscyamin) 
were  lor  a  time  rendered  ludicrously  "foolish"  v/ith 
all  the  symptoms  of  temporary  insanity.  Other 
chemicals  when  inhaled  are  well  known  to  laboratory 
workers  as  extraordinarily  and  permanently  dan- 
gerous to  the  mind.  Exhaustive,  patient  work  of 
the  chemist  side  by  side  with  the  medical  observer  is 
needed  to  bring  light  into  this  at  present  utterly 
dark,  unexplored  field.  The  hardening  of  arteries — 
the  common  enemy  of  man  after  he  had  passed  mid- 
dle age — again  is  very  strongly  suspected  of  being 
largely  dependent  on  little  understood  nutritional 

[42] 


factors.  With  its  resultant  serious  diseases — high 
blood  pressure,  kidney  and  heart  troubles — we  have 
here  again  an  invaluable  field  for  research  by  the 
painstaking  complete  analytical  methods  of  the 
chemist,  which  may  ultimately  give  the  physician  the 
knowledge  to  prevent  the  effect  and  its  consequences. 

IV.      Physical  Chemistry   and  Physics   in   the 
Service  of  Medicine. 

We  have  been  considering  thus  far  some  of  the 
accomplishments  and  the  more  numerous  problems 
in  the  service  of  medicine  of  only  one  of  the  two 
great  methods  of  attack  of  chemistry  in  the  great 
study  of  the  transformation  of  matter — namely,  of 
what  we  have  called  constructive  chemistry,  dealing 
with  the  minute  analysis  of  the  composition  of  mat- 
ter and  with  the  building  up  or  synthesis  of  matter 
on  the  basis  of  the  knowledge  thus  gained.  There 
is,  as  was  stated  at  the  outset,  a  second  equally  im- 
Ti    J  portant    method    of     attack — the 

Ij  .  study  of  the  functional  or  dynamic 

side  of  the  transformation  of  mat- 
ter— comparable,  as  will  be  recalled,  with  the  study 
by  our  visiting  Martians  of  the  life  pulsating  through 
our  million  edifices  in  New  York  City  as  contrasted 
with  the  study  of  the  structures  of  the  city  by  the 
architectural  group. 

This  phase  of  the  profound  study  of  the  trans- 
formation of  matter  is   called  physical  chemistry, 
p,     .    y         involving  the  applications  to  chemi- 
ChlmUtry        ^^^  change  of  principles  of  physics, 
the    fundamental    science    of    the 
transformation   of   energy    (of   forces,   of  motion, 
ttc.) .     It  concerns  itself  primarily  with  the  laws  of 
chemical  change,  the  limits  and  controls  of  action. 

[43] 


The  two  kinds  of  chemical  investigation  go  hand  in 
hand,  but  the  fields  are  so  enormous  and  difficult 
that  as  a  rule  men  are  specialists  in  one  field  or  the 
other  and  only  in  rare  instances  have  expert  knowl- 
edge in  both  fields.  Quite  obviously,  since  life  is 
dynamic,  medicine  must  call  into  its  services  the 
physical  chemist,  as  well  as  the  constructive  chemist, 
as  we  have  labelled  them. 

A  few  illustrations  of  past  accomplishments  and 

of  future  problems  must  suffice  in  the  attempt  to 

elucidate  the  innumerable  applications  of  physical 

J,,     J,.  chemistry  to  medicine.    The  great- 

Factor  ii^ife  ^^\  factor  distinguishing  dynamic 
action,  such  as  we  have  it  in  life, 
from  a  static  condition,  is  the  time  f actor ,  the  speed 
factor.  Life  is  dependent  in  an  unusual  degree  on 
the  proper,  fine  adjustment  of  the  time  relations  of  a 
great  many  interdependent  actions  in  the  body:  the 
rate  of  the  heart-beat  (the  pulse),  the  rate  of  respi- 
ration, the  rate  of  metabolism  (the  speed  with  which 
our  food  is  consumed  in  the  blood,  tissues,  etc.),  the 
rate  of  digestion,  the  rate  of  elimination  by  the  kid- 
neys, skin,  lungs,  etc.,  are  all  of  the  same  vital  im- 
portance to  the  smooth  working  of  the  healthy  body, 
as  in  any  engine  the  rate  of  the  flow  of  gas,  the  rate 
of  combustion,  the  movements  of  pistons,  valves, 
etc.,  are  for  the  smooth  and  perfect  working  of  the 
machine.  In  fact,  the  wonderfully  fine  adjustment 
of  these  speed  factors  in  our  bodies  to  the  needs  of 
life  and  their  marvelous  capacity  of  self-regulation 
and  readjustment  under  disturbed  conditions  form 
perhaps  the  most  impressive  element  of  life  when 
viewed  from  the  standpoint  of  its  material  trans- 
formations. 

It  is  the  physical  chemist  who  has  discovered  the 
[44] 


ni     .    I  i^L      •  *  laws  of  the  speed  of  chemical  action 
Physical  Chemist  i-i.ii     r  ^i,     ^-         r     ^ 

r,.  J  r        — on  which  all  of  the  time  factors 

Discovered  Laws      .     ,       ,      ,        ,  .       ^  i      j  j 

^  rr    I  1.         of  the  body  ultimately  depend — 
of  Health  ,        ,       i      •     i    i        •  ^       j-  • 

L         J  and  to  the  physical  chemist  medicine 

is  turning  for  aid  in  the  solution  of 
these  problems  in  the  control  of  health. 

As  an  elementary  illustration,  let  us  consider  diges- 
tion, in  which  we  are  all  concerned.     Anyone  inter- 
H    Ith  ested  in  the  question  of  the  speed 

^.       ,  of   digestion  can  prepare   a   very 

hard    boiled    egg    (lo    minutes), 
versus  ,         i  •         V  r  ^i 

y^  .  separate  the  white  of  egg  from  the 

^  ^j    ,  yolk  and  press  the  former  through 

and  the  •'        i  •     i      r     •  i        i  i 

^.       r.  any  kind  or  sieve  at  hand;  equal 

Time  r  actor  ^  ,  .  r  i  \  ?i 

portions    (teaspoonfuls)    are   then 

placed  in  three  glasses  of  water,  kept  at  body  tem- 
perature or  a  little  higher  ( ioo°  to  120°  Fahrenheit) 
by  being  placed  in  a  larger  vessel  of  warm  water, 
the  contents  of  the  three  glasses  being  stirred  by 
paddles  moved  with  the  aid  of  a  little  water  turbine 
or  a  small  electric  wheel.  The  three  tumblers  thus 
prepared  represent  artificial  stomachs.  To  the  one 
£rlass  is  added  both  pepsin  and  two  or  three  drops  of 
dilute  hydrochloric  acid,  to  the  second  only  the  acid 
and  to  the  third  only  the  pepsin.  If  the  higher  limit 
of  temperature  has  been  used  (120°),  the  observer 
will  note  in  about  an  hour  or  less  that  in  the  glass 
(stomach)  containing  both  pepsin  and  acid,  the  egg 
albumin  will  have  been  dissolved — digested — this 
representing  a  normal  stomach;  in  the  other  two 
glasses,  representing  dyspeptics  lacking  either  acid  or 
pepsin,  there  will  be  no  digestion,  that  is,  indigestion. 

^  . ,      J  r,      .         Now,  it  evidently  is  of  funda- 
Acid  and  Jrepsm  .  \  ^  . 

r      *'       AT  *    mental  importance  to  us  to  know 
t  unctions  I\ot  .    \  .  1       r         • 

WhoUyKnoum    accurately  just  what  the  functions 
of  the  acid  and  of  the  pepsin  are  in 
[45] 


speeding  up  (accelerating)  the  digestion  of  our  food; 
no  one  would  engage  as  chief  engineer  say  of  a  war 
vessel  or  ocean  liner  any  man  who  did  not  under- 
stand thoroughly  the  why  and  wherefore  for  every 
adjustment,  every  control  in  the  complicated  machine. 
And  here  we  have  in  the  (to  us)  most  precious 
machines,  our  bodies,  at  the  very  outset  an  action 
which  no  man,  physician  or  chemist,  has  to  this  day 
completely  elucidated — the  mechanism  of  the  action 
of  pepsin  and  acid  in  digesting  our  food  at  the  very 
first  stages  of  its  absorption  in  our  systems.  The 
physical  chemist  has  clearly  defined  the  laws  and 
mechanism  of  related  actions  with  acid  alone,  has 
made  great  progress  in  the  study  of  the  action  of 
accelerators  (catalyzers)  in  general:  naturally,  It 
win  be  to  the  physical  chemist  that  medicine  must 
turn  for  a  more  profound,  more  concentrated  attack 
on  this  problem  of  digestion  under  the  Influence  of 
acid  and  the  peculiar  digestive  ferment  called  pepsin. 

.      ,      ^  Pepsin  is  but  one  of  a  very  large 

Accelerators  ,  ^  ,  i 

^     ^    ,,.  number  or  accelerators  or  catalyz- 
LontroUms  „    .  i     •     n 

^  ers — called   enzymes   technically — 

which  are  the  speed  regulators  of 
all  of  our  body  functions.  The  digestion  of  our 
food  In  the  stomach  and  Intestinal  tract,  its  trans- 
formation Into  new  materials  in  our  blood,  and  its 
storage  in  our  organs.  Its  combustion  In  the  blood 
and  tissues,  all  are  subject  to  these  controlling  fac- 
tors. And  not  a  single  one  has  been  completely 
mastered  as  yet  by  the  mind  of  man. 

A  -J-*     Ajx    *  In    the    little    experiment    tried 

Acidity  Anects      .  .         .  r       •  t 

Ti    iJl  above,  the  absence  ot  acidity  was 

Health  ,         '  ,  .  i     i      •     i 

observed  to  be  quite  as  pathological 

as  the  absence  of  pepsin — and  as  a  matter  of  fact  the 

presence  or  absence  of  acidity,  or  In  certain  cases,  of 

[46] 


its  complement,  alkalinity — is  another  of  the  great 
controlling  factors  in  the  healthy  functioning  of  the 
body.  Proper  acidity  of  the  stomach  facilitates  diges- 
tion— acidity  of  the  blood  or  tissues  on  the  other 
hand  is  most  detrimental  to  combustion  of  our  food; 
hyperacidity  of  our  renal  secretions  can  be  of  the 
greatest  danger  to  the  secretory  organs,  the  kidneys. 
Self-Regulation  O^r  blood  has,  however,  a  re- 
of  the  Blood     markable  capacity  to  preserve  its 

and  Its  Physical-  ^^™^^  ^^'^^^  ^f^^^^  ^^  alkalinity, 
ru  '  1  to  escape  at  the  same  time  the 
Chemical         c     ^^  r     ^  •  j-  j       i 

ir*.«/«««*^;^«      bcylla    or    hyperacidity    and    the 
txplanaUon  ^  /^  .    ^ 

Lharybdis  of  excessive  alkalinity. 
This  wonderful  capacity  for  self-adjustment  and 
preservation  of  its  optimum  conditions  for  the  pur- 
poses of  life  is  a  typical  instance  of  innumerable  fine 
mechanisms  of  self-adjustment  in  the  body,  all  aimed 
at  maintaining  the  most  favorable  environment  for 
the  functioning  and  preservation  of  life  —  self- 
adjusting  mechanisms  which  in  fact  comprise  for  the 
scientific  investigator  the  most  impressive  points  of 
difference  between  living  organisms  and  the  lifeless 
world.  And  yet  this  remarkable  power  of  the  blood 
to  maintain  its  normal  alkalinity  has  been  elucidated 
in  a  very  complete  way  (especially  by  L.  Henderson 
of  Harvard  University)  by  the  application  of  simple 
principles  of  physical  chemistry  to  the  study  of  the 
composition  of  the  blood:  There  are  chemical 
^'buffers*'  present,  which  act  chemically  to  preserve 
neutrality  exactly  as  powerful  springs  act  as  mechan- 
ical buffers  to  minimize  the  shock  of  impact  to  fast 
moving  bodies. 

It  is  well  for  us  to  recall,  moreover,  that  the  last 
generation  of  scientific  workers  could  not  possibly 
have  elucidated  this  wonderful  mechanism  of  self- 

[47] 


adjustment,  for  the  simple  reason  that  the  discoveries 
of  the  necessary  fundamental  facts  and  principles  of 
physical  chemistry  which  Henderson  applied,  simple 
as  they  are,  had  not  yet  been  made.  We  must  bear 
this  lesson  in  mind  when  we  face  other  mechanisms 
of  fine  self-adjustment  for  which  at  present  we  may 
be  at  a  loss  to  find  the  key. 

B  d    W    h  Another  question  of  peculiar  in- 

c  L  •  *  ^  terest  to  man  as  a  worker  is  the 
p,  .  ,  problem  or  the  conversion  of  fuel 
J  elements   in   our   food   into  work, 

comparable  with  the  problem  of 
the  efficiency  of  the  coal  or  oil  consuming  steam  en- 
gine or  of  the  internal  combustion  engine.  This  is 
essentially  a  problem  of  physics,  the  fundamental 
science  of  the  transformation  of  energy.  Mayer 
more  than  sixty  years  ago  called  attention  in  general 
terms  to  the  sources  of  energy  for  body  work  and 
emphasized  the  fact  that  living  organisms  are  sub- 
ject to  the  great  physical  law  of  the  conservation 
of  energy.  In  very  recent  years  A.  V.  Hill  of  the 
University  of  Manchester  has  succeeded  in  applying 
in  a  masterly  way  the  laws  of  physics  in  great  detail 
to  the  working  of  a  muscle. 

It  is  work  of  this  character,  leading  step  by  step 
to  the  complete  understanding  of  most  complex 
actions  of  our  body  by  the  application  of  the  prin- 
ciples of  physics  and  chemistry,  which  sustains  the 
faith  of  those  who  believe  that  chemists  and  physi- 
cists, working  in  closest  cooperation  with  the  experts 
in  the  various  fields  of  biology,  will  ultimately  ex- 
press all  the  major  facts  of  the  material  side  of  life 
in  their  own  exact  terms  and  thereby  give  to  medicine 
the  control  characteristic  of  an  exact  science.  How 
necessary  such  encouragement  of  the  faithful  army 

[48] 


of  scientific  workers  is,  must  be  apparent  from  the 

^  ..         .  way  in  which  so  eminent  a  physi- 

Looperatwn  to  ,.             ttu             r  r\   r     a    - 

„            w  .  ologist  as  Haldane  of  Oxford,  m 

Express  Major  .^       .    ,  .                ,    .,i.                 , 

„^        .  J .,  spite    of   his   own   bnlhant   work, 

carried  out  with  the  aid  of  physics 
and  chemistry,  on  the  fine  adjustment  of  respiration 
to  environment,  despairs  of  the  complete  success  of 
the  fundamental  sciences  in  explaining  the  automatic 
adaptation  of  the  body  to  its  life  needs  and  to  its  own 
reproduction,  and  falls  back  on  metaphysical  con- 
ceptions.^ 

We  need  but  recall  that  every  modern  machine, 
from  the  power  engine  to  the  loom,  from  the  printing- 
press  to  the  watch,  is  equipped  with  numberless  auto- 
matically working  devices  of  fine  control  and  self- 
adjustment  (such  as  the  self-adjustment  of  a  fine 
watch  to  temperature  changes,  by  which  winter  and 
summer  alike  it  will  not  vary  a  second  in  the  ticking 
off  of  time.  To  the  barbarian  these  man-made  ma- 
chines are  as  wonderful  and  complex,  because  not 
understood,  as  are  indeed  the  marvelously  fine  and 
sensitive  powers  of  adjustment  of  the  living  organism 
to  us,  who  still  understand  so  little  about  them.  Our 
problem  without  question  is  a  tremendously  complex 
one,  but  the  advances  already  made  are  a  sufficiently 
brilliant  promise  of  ultimate  success,  and  we  can  best 
hasten  the  advance  by  bringing  together  for  closest 
cooperative  work  expert  workers  to  form  a  small, 
well-organized  corps,  where  in  the  past  advance  has 
depended  most  largely  on  the  brilliant  but  dispersed 
sorties  of  the  individual  worker. 

Colloidal  ^  further  field  of  investigation 

Chemistry        ^^^  ^^^  physical  chemist,  which  is 

of   major   importance   to    the    de- 

^ Haldane,  Mechanism,  Life  and  Personality,  1914,  and  Organism 
and  Environment,  1916. 

[49] 


velopment  of  medicine  as  an  exact  science  rather 
than  an  art,  is  the  study  of  "colloids."  Graham 
distinguished  crystalline  substances  such  as  salt  or 
sugar,  from  what  he  was  the  first  to  term  colloids 
(from  coile,  the  Latin  for  glue) .  Now  the  vital  fact 
about  colloids  is  that  they  do  not  dissolve  as  would 
salt  or  sugar  say,  in  water,  but  colloids  form  sus- 
pensions :  milk  is  a  common  illustration  of  such  a 
suspension  of  fat  globules  and  of  the  cheesy  com- 
ponents (casein)  in  a  watery  solution  of  milk  sugar 
and  some  salts.  Clay  stirred  up  in  water  represents 
another  well-known  suspension.     But  the  most  im- 

«,,     „  portant  instance  of  colloids  is  the 

1  he  Human       f  i      i      •      ir       n      r     i 

n    1    J  human  body  itself,  all  of  the  tis- 

r  llnd  1  sues,  muscles,  fluids  of  which  rep- 
resent colloidal  suspensions.  It  is 
for  that  reason  that  the  exhaustive  study  of  colloidal 
chemistry  is  of  vital  importance  for  the  develop- 
ment of  medicine  as  a  science.  Two  or  three  specific 
illustrations  of  the  nature  of  the  problems  we  are 
facing  must  suffice  here.  It  is  well  known  to  all  of 
us  that  the  very  stability  of  such  a  colloidal  system 

T>  j'1    c*  1--7-*     as  milk  is  subject  to  disturbance  by 
Bodily  Stability  ,,    ,  •'.      ,  .  t- 

c      '^-  small  changes  m  the  system;  acidity 

Sensitive  ,  •      \      t      i  i     • 

(souring)     leads    to    coagulation, 

time  or  churning  leads  to  the  separation  of  cream  and 
eventually  of  the  butter.  In  either  event,  the  milk  as 
such  is  destroyed.  All  colloidal  systems,  and  espe- 
cially those  of  the  body,  are  similarly  sensitive  to 
forces  affecting  their  stability:  the  kidneys  are  pecu- 
liarly sensitive  to  acidity;  the  coagulation  of  our 
blood,  the  stiffness  of  our  muscles  are  instances  of 
disturbances  of  colloidal  systems  vital  to  our  health. 
Milder  disturbances  lead  to  ill-health,  severe  changes, 
as  the  injection  of  acid  into  our  veins,  lead  to  death. 

[50] 


Besides  the  question  of  stability  of  our  colloidal 
organs,  tissues  and  fluids,  another  vital  consider- 
ation is  this :  Since  a  colloidal  system  represents  a  sus- 
pension, we  are  dealing  in  every  Instance  with  at  least 
two  and  often  many  more,  different  media  of  en- 
tirely different  properties.  As  the  dweller  on  one  of 
the  Thousand  Islands  must  live  with  the  problem  of 
water  as  well  as  of  land,  and  must  arrange  for  a 
system  of  communication  by  water  and  by  land,  so 
on  the  other  hand  the  scientific  study  of  our  body  is 
leading  us  to  discriminate  carefully  between  the  needs 
of  the  watery  fluids  of  the  body  and  of  the  dozen 
different  suspensions  in  us,  fatty,  gelatinous,  protein- 
like, etc. 

c    /  Surface    properties    of    colloids 

burface  .  ,•     ,  •      -r 

Eif    t  ^^^        peculiarly  great  signihcance 

In  life  reactions — comparable 
roughly  with  the  importance  of  shore  facilities,  of 
shore  stability,  to  our  typical  island  inhabitant.  Sur- 
face tension,  the  force  which  makes  the  film  of  a 
soap  bubble  round  and  which  may  preserve  it  Intact 
even  when  pricked  by  a  fine  needle,  is  found  by  physi- 
cists to  vary  greatly  under  stimuli  such  as  electrical 
charges  or  chemical  changes.  It  is  known  to  play  a 
fundamental  role  In  life  reactions  such  as  in  the  mo- 
tions of  lower  organisms,  and  the  principles  of  sur- 
face tension  must  find  a  wide  field  of  application  in 
the  study  of  the  complex  suspensions  of  our  own 
bodies. 

Th   P    hU*  Perhaps  of  even  greater  need  of 

,  r,         .  profound  study  are  the  adsorption 

and  absorption  phenomena  of  sur- 
faces bathed  by  liquids :  thus  our  organs  of  secre- 
tion, all  colloids,  have  truly  marvelous  powers  of 
maintaining  conditions  In  the  body  favorable  to  life. 

[51] 


For  instance,  the  kidneys  will  prevent  in  very  larg- 
est measure  the  diluting  of  our  blood  even  when 
large  volumes  of  water  are  imbibed:  they  respond 
at  once,  eliminating  the  superfluous  water  into  the 
bladder  as  quickly  as  it  is  absorbed.  In  like  fashion 
they  rapidly  eliminate  excessive,  injurious  amounts 
of  sugar,  salt  and  other  products  liable  to  modify 
the  character  of  the  blood.  The  mechanism  of  se- 
lective secretion  by  the  kidney,  the  mechanism,  in 
fact,  of  secretion  by  any  organ,  is,  in  spite  of  many 
important  investigations  and  their  partial  answers, 
still  mainly  an  unsolved  riddle  to  science.  And  yet 
there  is  no  problem  of  greater  importance  to  health 
in  view  of  the  vital  role  played  by  our  organs  of 
secretion. 
f>         p       '  A  more  profound  and  exhaustive 

.    .  J  fundamental  study  of  colloids  holds 

of  Advance  ,  .  •         r     j 

out  the  greatest  promise  or  advance 

in  this  direction:  let  us  recall  that  the  neutrality 
of  our  blood  could  only  be  explained  after  physical 
chemistry  had  advan^^d  sufficiently  to  give  us  the 
theory  of  "buffer'*  neutralizing  agents,  one  of  the 
consequences  of  the  Arrhenius  theory  of  ionization 
— a  great  and  unknown  field  before  the  year  1887. 
Likewise  the  great  problem  of  selective  absorption 
by  colloid  organs  is  probably  awaiting  further 
advances  in  the  fundamental  sciences  themselves. 
It  must  be  quite  obvious  that  a  concentrated  at- 
tack on  the  problems  of  health  and  disease  from  the 
point  of  view  of  the  fundamental  sciences  of  chem- 
istry and  physics  must  include  intensive  study  of  the 
colloidal  systems  which  form  the  major  structure  of 
our  bodies. 


[521 


V.  The  Fundamental  Problem — The  Chemistry  of 
the  Body  Cells 
In  outlining  the  methods  by  which  the  funda- 
mental sciences  of  chemistry  and  physics  could  con- 
tribute to  the  raising  of  medicine  to  the  plane  of  an 
exact  science  in  maintaining  health  and  curing  dis- 
ease, we  have  thus  far  emphasized  the  possibilities 
for  the  solution  of  a  number  of  specific  and  urgent 
problems,  which,  however  difficult,  hold  out  the 
promise  of  definite  and  not  too  remote  success  in  a 
coordinated  attack  upon  them  by  chemistry,  physics 
and  medicine:  the  preparation  of  specific  remedies 
for  specific  diseases,  the  isolation  of  pure  principles 
as  swift,  sure  weapons  to  be  placed  in  the  hands  of 
the  practitioner,  the  protection  of  health  by  the  ex- 
haustive analysis  of  food,  the  profound  study  of 
our  time  reactions  and  their  regulators,  the  study 
of  colloids  as  the  basis  of  investigation  of  our  organs 
of  secretion,  are  some  of  the  points  of  vantage 
toward  which  most  likely  the  .surest  approach  could 
be  made.  Success  in  these  directions  would  bring 
unmeasured  blessings  to  mankmS  in  the  prevention 
and  cure  of  disease  and  the  consequent  promotion 
of  happiness. 

TL    rz     s.   t         But  the  very  heart  of  the  prob- 
1  he  Heart  of      .  r  t-r        i       i-   i  r  r 

th    P    hi     -—       "^  ^    '  highest  form  or 

Th  C  II  chemical  change,  lies  in  the  pro- 
found and  complete  study  of  the 
chemistry  of  the  body  cells,  the  units  of  which  our 
bodies  are  composed.  This  is  the  most  important, 
and  also  by  far  the  most  difficult  problem  of  all: 
Its  solution  is  vitally  necessary  for  that  ultimate  com- 
plete mastery  of  science  over  life,  which  will  give 
man  the  wisdom  to  maintain  health  ana  increase  the 
life  span  of  the  greatest  number. 

[53] 


rpf^    Tj  If  we  let  our  minds  dwell  on  the 

B  d    E    f>d         complexity  of  our  body's  structure 
r  II  Li  ^^^  functions,  we  must  recognize 

without  question  that  man's  body  is 
not  a  primary  form  of  life  but  the  result  of  the  slow 
processes  of  evolution  from  simpler  forms  through 
the  ages.  The  whole  history  of  the  human  race  is 
indeed  revealed  to  us  in  the  most  impressive  fashion 
by  the  development  of  the  embryo,  starting  with  the 
fecundation  of  the  minute  human  ovum,  a  single  cell, 
and  growing  slowly  by  a  rapid  multiplication  of  cells 
to  the  fully  developed  infant  as  it  appears  at  birth. 
Our  bodies  are,  in  fact,  wonderfully  organized  com- 
munities of  myriads  of  cells,  the  primal  form  of  life. 
And  all  of  our  life  functions  are  still  carried  out  as 
in  primal  days  by  cell  secretion,  cell  excretion  and 
cell  multiplication — the  change  of  our  food  into  body 
tissues,  the  elimination  of  waste  products,  the  devel- 
opment of  the  means  of  procreation  are  but  instances 
of  this  general  truth  regarding  our  body  activities. 
Except  for  the  extreme  differentiation  of  functions 
of  special  cells,  we  still  live  solely  through  the  co- 
ordinated activities  of  cells. 
jy.         ^,  As  a  result  the  problem  of  curing 

r  II  I  ^^  preventing  disease  is  tending  in 

T^.  ^    ,  an  important  sense  toward  a  study 

Visturbance  r    i  %         i  •  i  j*  • 

of  the  means  by  which  conditions 

for  normal  cell  processes  may  be  maintained  or  re- 
stored after  any  disturbance.  In  other  words,  we 
are  being  forced  to  conclude  that  the  seat  of  dis- 
turbances leading  to  disease  is  the  living  cell  which 
the  biologist  justly  conceives  as  the  unit  of  biological 
change.  An  active  and  normal  cell  development 
therefore  means  good  health.  These  activities  are 
fundamentally  chemical  and  physical  in  character. 

[54] 


Let  us  recall  again:  "Cell-secretion,  cell-respiration 
and  cell-nutrition  are  clearly  only  different  aspects  of 
the  whirl  of  molecular  activity"  and  "there  is  a  con- 
stant molecular  interchange  between  the  cell  and  its 
environment."  It  is  physics  and  chemistry  that  study 
natural  phenomena  from  the  point  of  view  of  molec- 
ular activities — it  is  to  physics  and  chemistry  that 
biology  must  turn  for  the  ultimate  study  of  its  units 
of  life,  the  cells,  and  we  cannot  overemphasize  the 
importance  of  increasing  our  knowledge  of  the  mech- 
anism of  the  chemical  processes  operating  In  these 
hidden  laboratories  wherein  all  the  fundamental  re- 
actions of  life  originate  and  take  place. 

^      J  Now,  while  multitudes  of  definite 

Our  Ignorance      ,        .     ,       ,  i  , 

,   ,  chemical  substances  have  been  iso- 

^,      .  ^         lated  from  animal  and  veeretable 
Chemistry  .  ,       .  ,       .^       .  r      i  •  i 

I  ^i.    r>  11       tissues,  the  identification  or  which 
oj  the  Cell        .  '      .,      .  111 

IS  a  contribution  to  our  knowledge 

of  the  chemistry  of  the  cell,  no  comprehensive  and 
exhaustive  study  of  the  contents  of  even  a  single 
type  of  cell  has  ever  been  attempted.     In  fact,  it  is 
only  when  we  begin  to  consider  the   cell  from   a 
strictly  chemical  point  of  view  that  we  are  led  to 
recognize  how  scanty  indeed  is  our  knowledge  of 
the  chemistry  of  this  vital  biological  unit.     Thus, 
Livins  and       ^^  ^^  "^^  ^^^"  know  in  exact  terms 
Lifelels  Material  ^J  P^^^^"  ^"5^  chemistry  what  the 
Undiscovered      ^^^^^^\  ^^^  that  distinguish  living 
from  lifeless  material:    What  are 
indeed  the  chemical  and  physical  forces  that  lead  to 
cell  subdivision,  the  wonderful  first  step  in  life  de- 
velopment?   What  are  the  forces  that  lead  to  per- 
petuation of  life?     To   instinctive  self-protection? 
What  are  the  conditions  for  the  equilibrium  in  the 
colloidal  system  we  call  protoplasm,  which  make  an 

[55] 


obvious  difference  between  life  and  death?    What 
is  the  chemical  structure  of  proteins?    Of  the  com- 
ponents of  brain  tissue,  underlying  the  most  won- 
derful of  all  life  processes,  consciousness,  memory, 
What  of         thought,  and  feeling?    What  is  the 
Heredity         chemistry   or   the    physics    of   the 
inheritance    of    body    form    from 
generation  to  generation,  even  of  the  finer  traits  of 
mind  and  temperament  carried  from  parent  to  child 
through  the  minute  cells  of  procreation?    Are  some 
of  the  millions  of  chemical  molecules  present  even  in 
these  minute  cells  in  some  way  the  carriers  of  this 
wonderfully  accurate  transmission  of  qualities? 

TJ.«  p^  ,^   ^i         These  are  but  a  few  of  the  extra- 
1  he  rower  of  ,.        .,      .  ,,  - 

Knowledge  ^rdmarily  important  problems  of 
versus  Theory  chemistry  and  physics  in  the  ulti- 
mate  field  of  cell  life.  They  are 
tremendous  problems  but  many  believe  they  are  not 
beyond  the  power  of  the  human  mind  in  control  of 
the  scientific  tools  of  chemistry  and  physics.  Indeed, 
until  these  exact  sciences  do  shed  more  light  on  these 
problems,  there  will  be  speculation,  theory,  philoso- 
phizing— but  not  knowledge.  It  will  take  many  gen- 
erations of  many  workers  to  attain  this  knowledge, 
but  who  can  question  for  a  moment  that  complete 
success  in  these  problems  would  spell  for  mankind 
health  of  the  body,  health  of  the  mind,  and  the  hap- 
piness of  untold  millions  of  sensitive  beings!  And 
based  on  this  knowledge,  the  medicine  of  the  future 
will  finally  succeed  in  attaining  its  present  noble  goal, 
to  prevent  disease,  to  maintain  health,  so  that  to  a 
less  degree  there  will  be  need  of  the  combatting  of 
disease. 


fS6] 


EXISTING   FACILITIES   FOR   CHEMO- 
MEDICAL  RESEARCH 

In  order  to  form  a  correct  judgment  in  regard  to 
the  necessity  for  chemo-medical  research,  it  is  essen- 
tial to  make  a  survey  of  the  facilities  now  available 
in  this  country  and  contrast  them  with  the  facilities 
existing  in  other  countries. 

Our  own  country,  with  its  vast  resources,  should 

have  a  leading  part  in  this  important  field  of  work; 

we  cannot  at  this  time  escape  the  responsibility  for 

contributing   our   full  share  to  the   alleviation   of 

human  suffering  caused  by  disease,  yet  if  we  compare 

the  number  and  scope  of  our  own  institutions  for 

medical  research  with  those  of  other  countries  it  is 

evident  that  much  remains  to  be  done  before  we  can 

aspire  to  leadership  in  this  branch  of  research. 

p    .,.^  In    commenting    on    Ehrlich*9 

.      ,  work  in   19 13,  a  popular  maga- 

TT  •*  J  c*  *  zine^  said:     "More  immediately 

United  States  .     t    1  1  •      -/ 

practical  than  any  other  scientmc 

development  of  our  time  is  the  subjection  of  the 
science  of  medicine  to  the  principles  of  chemistry. 
.  .  .  The  importance  of  regarding  medicine  as  a 
branch  of  chemistry  and  not  as  an  independent  sci- 
ence is  manifest  when  we  remember  the  therapeutic 
mysteries  for  a  solution  of  which  mankind  is  now 
desperately  groping."  The  value  of  fundamental 
studies  in  relation  to  disease  has  thus  been  more  or 
less  generally  recognized  for  a  number  of  years, 

'  Current  Opinioo  55-256. 

[57] 


yet  our  survey  shows  that  at  the  present  time  we 

are  far  behind  Europe  in  our  facilities  for  chemical 

research. 

^L      .    ,  While  there  are  in  the  United 

Chemical  ^  i  r   •       •  i 

e^     7     .  ^       btates  a  number  or  mstitutes  and 

otancipomt  r  1      •  e  t      i  ^ 

J     f.  toundations   tor  medical   research 

doing  most  valuable  work,  there  is 
none  in  which  the  problems  are  being  approached 
primarily  from  the  chemical  standpoint.  Conse- 
quently few  new  lines  of  chemical  investigation  in 
relation  to  disease  have  been  developed  in  this  coun- 
try and  we  have  been  largely  dependent  upon  foreign 
countries,  especially  Germany,  for  discoveries  relat- 
ing to  the  applications  of  chemistry  to  disease.  In 
considering  the  publications  relating  to  chemo- 
therapy which  have  appeared  in  this  country,  it  is 
remarkable  to  what  a  large  extent  they  have  followed 
a  few  lines  opened  up  in  Europe.  Thus  the  many 
investigations  on  the  therapeutic  value  of  the  newer 
arsenic  compounds ;  the  very  numerous  studies  on  the 
action  of  aniline  dyes,  including  the  combination  of 
these  with  mercury  and  other  metals  and  the  work 
on  the  effects  of  quinine  derivatives  in  pneumonia, 
are  all  based  upon  the  work  of  Ehrlich.  When 
Ehrlich  laid  the  foundations  for  this  work  he  was 
occupied  with  certain  broad  general  problems  (such 
as  the  laws  governing  the  distribution  of  chemical 
compounds  in  the  body)  and  not  with  specific  dis- 
eases. Work  along  these  lines  is  already  beginning 
to  stagnate,  and  it  is  becoming  more  and  more 
evident  that  new  points  of  view  are  needed  which 
can  be  obtained  only  by  a  return  to  the  study  of 
fundamentals. 

It  will  be  noted  that  many  of  the  research  founda- 
tions in  this  country  have  been  established  for  the 

[58] 


study  of  certain  diseases,  or  classes  of  diseases,  and 
are  not  therefore  free  to  work  upon  broad,  funda- 
mental problems.^ 

Institutes  and  Laboratories  in  the  United  States 
In  the  United  States,  medical  research  is  conducted 
in  universities,  special  institutes,  Government  labora- 
tories and  industrial  establishments. 

Med'  al  Many  of  the  leading  University 

p  ,    .         Medical  Schools,   although   by  no 

.       .  means    all,    have    departments    or 

American  ^,  '  ,.       f  -j 

jj  .       .  .  Pharmacology.     In  these  a  consid- 

erable amount  of  valuable  investi- 
gation on  the  action  of  chemical  substances  in  health 
and  disease  is  being  done.  Little  of  this  investiga- 
tion, however,  relates  to  fundamental  subjects;  it 
consists    rather    in    the    detailed    study    of     some 

*The  importance,  even  for  the  solution  of  immediately  practical 
problems,  of  opportunities  to  pursue  fundamental  studies  irrespec- 
tive of  any  specific  disease  is  strikingly  shown  by  the  circumstances 
leading  to  the  discovery  of  arsphenamine.  Ehrlich  was  engaged  in 
a  study  of  the  chemical  and  physical  principles  which  determine 
the  distribution  of  compounds  in  the  animal  body  and  had  selected 
the  study  of  dyes  since  their  distribution  was  easily  determined. 
While  the  purpose  of  these  studies  was  purely  theoretical,  Ehrlich 
found  that  some  of  the  dyes  seemed  to  have  a  special  affinity  for 
blood  corpuscles  and  thought  that  they  might  be  of  value  in  malaria. 
He  accordingly  made  a  series  of  experiments  upon  bird  malaria 
and  afterward  determined  the  effects  of  the  dyes  upon  parasites 
somewhat  similar  to  those  of  malaria,  viz.,  trypanosomes.  Only 
after  he  had  found  what  chemical  groups  made  the  dyes  injurious 
to  the  parasites  did  he  take  up  the  study  of  arsenic  compounds. 
He  prepared  compounds  containing  arsenic  very  similar,  chemi- 
cally, to  some  of  the  dyes  and  found  that  the  same  laws  governed 
their  trypanocidal  action.  He  next  tried  these  compounds  upon 
the  organism  of  syphilis  which  at  that  time  was  supposed  to  belong 
to  the  group  of  trypanosomes.  In  this  way,  from  a  purely  theo- 
retical study,  Ehrlich  was  led  to  the  discovery  of  "606." 

If  the  activities  of  Ehrlich  had  been  restricted  either  by  the 
Government  or  by  the  terms  of  a  bequest  to  a  study  of  dyes  or 
of  arsenic  compounds,  or,  on  the  other  hand,  to  an  effort  to  dis- 
cover a  remedy  for  sleeping  sickness  or  for  syphilis,  it  is  not  very 
probable  that  he  would  have  been  led  to  the  discovery  of  the 
value  of  certain  arsenic  compounds  in  the  treatment  of  syphilis. 

[59] 


substance,  usually  a  well-known  chemical  compound, 

upon  some  highly  specialized  tissue  or  organ.  Among 

the  more  fundamental  subjects  investigated  in  these 

laboratories   may   be   mentioned   pioneer  work   on 

epinephrine  (adrenalin)  and  on  the  local  anaesthetic 

properties  of  aromatic  alcohols. 

y    _.      .  The  primary  purpose   of  these 

Instruction  ,   .            ^ .       .  -^    ^     \              .           - 

r '    .^  ,.  laboratories   is  the   instruction   of 

Limitations  ,.     i        j              i  •  i      /• 

^  medical  students,  which  or  necessity 

forces  the  staffs  to  cover  a  wide 
field;  this  and  the  various  other  duties  connected  with 
an  academic  position  allow  comparatively  little  time 
for  concentrated  work  on  problems  of  major  impor- 
tance. Moreover,  most  of  these  departments  are  not 
in  close  touch  with  departments  of  chemistry,  as  the 
university  pharmacologist  and  chemist  are  usually 
interested  in  chemical  compounds  from  entirely  dif- 
ferent points  of  view:  the  pharmacologist  from  the 
standpoint  of  the  therapeutist  and  physiologist,  and 
the  chemist  from  the  standpoint  of  some  general 
chemical  principle.  Exactly  the  same  difficulties 
stand  in  the  way  of  departments  of  bio-chemistry 
(physiological  chemistry)  as  organized  in  most  uni- 
versities: primarily  interested  in  the  instruction  of 
medical  students,  they  are  doing  praiseworthy  work, 
but  necessarily  limited  in  scope. 

These  circumstances,  taken  in  connection  with  the 
comparatively  limited  resources  of  the  universities, 
make  it  improbable  that  the  character  of  work  in 
the  minds  of  the  committee  can  be  satisfactorily 
accomplished  in  university  laboratories. 

As  an  instance  of  the  severe  handicaps  placed  on 
the  University  worker,  the  following  is  of  interest: 
In  1 910  a  pharmacologist  in  one  of  our  leading  uni- 
versities discovered  and  isolated  from  the  contents 

[60] 


of  the  poison  glands  of  the  tropi:al  toad  bufo  agua 

a  pure  chemical  principle,  bufagii;,  which  was  found 

to  have  a  marked  and  important  action  on  the  heart, 

^  ^  of  the  order  of  the  most  effective 

.  members    or    the    digitalis    series. 

American         ^t  j-   •     i-    •      i  t     i  « 

^.  JNow,  digitalis  is  the  most  valuable 

heart  stimulant  known  to  medicine, 
but  it  consists  of  a  mixture  of  principles  and  it  is  one  of 
the  most  unsatisfactory  of  drugs  to  handle,  because  of 
the  difficulties  of  securing  uniform  preparations  of  It, 
on  whose  effects  the  physician  may  count  with  absolute 
certainty.  It  is  also  difficult  to  secure  reliable  prepa- 
rations for  hypodermic  injections  with  their  advan- 
tages of  almost  instantaneous  results.  A  pure  chemi- 
cal principle  with  the  same  action  on  the  heart  as 
digitalis  would  be  free  from  all  of  these  vital  defects 
and  would  prove  an  invaluable  addition  to  our  ma- 
teria medica.  With  the  limited  resources  in  per- 
sonnel, supplies,  etc.,  our  university  men  have  not 
been  able  to  develop  this  promising  investigation  by 
any  large  scale  preparation,  and  now  a  German 
chemist,  with  the  munificent  support  of  German 
chemical  industries,  is  moving  at  top  speed  to  isolate 
in  quantity  and  commercialize  a  similar  principle 
found  In  a  species  of  German  toad. 

It  was  doubtless  the  limitations  of  research  in  the 
medical  schools  which  led  to  the  founding  of  a  con- 
siderable number  of  institutes  for  medical  research; 
some  of  these  are  In  connection  with  universities  or 
hospitals,  while  others  are  entirely  Independent. 

The  largest  and  most  prominent  of  these  institutes 
is  the  Rockefeller  Institute  for  Medical  Research, 
The  staff  of  this  Institute  consists  of  ten  ''members" 
with  their  associates  and  assistants.  Eight  of  these 
"members"  are  occupied  with  studies  on  bacteriology, 

[61] 


pathology,    immunology,    serology,    general    physi- 
ology,   diseases    of   animals,    experimental    surgery, 
clinical  researches  on  diabetes,  heart  disease,  kidney 
disease,  pneumonia,  yellow  fever, 
bpecial  meningitis,  infantile  paralysis,  etc. 

'^^i  ",.^^  ,  Iri  the  fall  of  1920  announcement 

Medical  1       1         j     •          1 

„           ,  was  made  that  durmg  the  ensumg 

Research  .           ,      r  n       •       j-                     ij 

in  the  wmter  the  tollowmg  diseases  would 

United  States  be  made  the  subject  of  special  study 
at  the  institute:  acute  lobar  pneumo- 
nia and  other  acute  pulmonary  infections,  measles, 
acute  rheumatic  fever,  cardiac  disease  and  nephritis. 
Two  "members"  devote  their  time  to  chemical  work. 
The  activities  of  the  one  relate  largely  to  the  structural 
chemistry  of  nucleic  acids,  lipoids,  and  other  impor- 
tant components  of  the  body.  Under  this  "member," 
also,  are  chemists  whose  work  relates  to  chemo- 
therapy; their  researches  have  extended  to  such  com- 
pounds as  derivatives  of  hexamethylenetetramine,  of 
certain  arsenic  acids  and  of  quinine.  A  number  of 
these  derivatives  have  been  tested  in  other  divisions 
of  the  institute  and  in  the  hospital,  for  their  thera- 
peutic action.  The  other  chemical  "member"  works 
in  connection  with  the  hospital  of  the  institute,  and 
his  work  at  present  relates  chiefly  to  refinements  in 
the  methods  of  blood  analysis  and  other  methods  of 
clinical  interest.  A  third  "member"  of  the  institute 
is  working  on  the  fundamental  theory  of  colloids 
and  the  application  of  other  physical  relations  to  life 
phenomena.  Part  of  the  excellent  work  of  this  in- 
stitute is  in  the  direction  of  our  chief  aims,  but  the 
emphasis  is  rather  placed  on  the  pathological  and 
other  medical  features  of  the  problems  than  on  the 

[62] 


direct  attack  on  the  problems  of  medicine  by  means 
of  a  concerted,  wholly  cooperative  effort  of  leaders 
in  the  fundamental  sciences  of  chemistry  and  physics, 
in  pharmacology  and  in  medicine. 

The  Otho  S.  A,  Sprague  Memorial  Institute^ 
which  is  closely  affiliated  with  the  University  of  Chi- 
cago, covers  in  part  the  same  class  of  problems  as 
does  the  Rockefeller  Institute,  but  rather  more  em- 
phasis is  placed  upon  the  chemical  aspects  of  medical 
problems.  The  Sprague  Institute  has  no  buildings 
of  its  own,  but  cooperates  "with  existing  institutions 
wherever  and  whenever  it  seems  that  medical  re- 
search can  be  furthered."  In  pursuance  of  this 
policy  it  supports  work  in  various  laboratories  of  the 
University  of  Chicago  and  in  several  hospitals. 
Among  the  major  problems  studied  are  cancer,  dia- 
betes, chronic  articular  rheumatism,  dementia  precox, 
occupational  and  children's  diseases.  Among  the 
more  strictly  chemical  studies  may  be  mentioned  a 
series  of  investigations  on  the  chemistry  of  the 
tubercle  bacillus;  studies  on  the  chemical  aspects  of 
diabetes  and  gout,  of  immunology,  of  protein  therapy 
and  of  the  amines  obtained  from  proteins. 

Only  about  half  of  the  members  of  the  staff  give 
full  time  to  the  Institute ;  the  others  are  engaged  also 
in  the  practice  of  medicine  or  in  teaching.  Excellent 
as  is  the  work  being  performed,  there  is  no  intensive, 
concerted  attack  on  problems  by  any  such  group  of 
experts  as  is  contemplated  in  this  report. 

The  John  McCormick  Institute  for  Infectious  Dis- 
eases is  also  located  in  Chicago;  its  problems  arc 
chiefly  connected  with  those  of  infection  and  im- 
munity. 

[63] 


i^*L     p    -T**,*^.        There  are  a  number  of  other 

Other  Facilities  .      .  ,  ,  ,  .       . 

,  r   ,       ^    .  institutes  and  laboratories  in  con- 
ana  Laboratories            .              .  I  Till  1 

nection  with  medical  schools  and 
hospitals,  founded  for  medical  research,  such  as  the 
Mayo  Foundation,  Rochester,  Minn.,  the  George 
Williams  Hooper  Foundation  for  Medical  Research 
of  the  University  of  California  Medical  School,  the 
Nelson  Morris  Memorial  Institute  for  Medical  Re- 
search of  the  Michael  Reese  Hospital  in  Chicago, 
the  H,  K,  Gushing  Laboratory  of  Experimental 
Medicine  at  Western  Reserve  University,  The  John 
Herr  Musser  Department  of  Research  Medicine  of 
the  University  of  Pennsylvania,  the  Bender  Hygienic 
Laboratory  at  Albany,  and  the  Harriman  Research 
Laboratory  at  the  Roosevelt  Hospital  in  New  York. 
^     ,      ,  In    addition    to    the    above- 

c      .  1  ri-  mentioned  laboratories  and  general 

bpecial  Diseases    .       .  ^  ,.     ,  ,     , 

institutes  tor  medical  research  there 

are  a  number  of  institutes,  laboratories,  funds  and 
foundations  for  the  study  of  special  diseases.  Among 
these  may  be  mentioned  the  following  for  the  study 
of  cancer:  the  George  Crocker  Special  Research 
Fund  at  Columbia  University,  the  Huntington  Funds 
for  Gancer  Research  at  the  Memorial  Hospital,  New 
York,  and  at  the  Harvard, Medical  School,  the  Gan- 
cer Laboratory  of  the  New  York  State  Department 
of  Health  at  Buffalo  and  the  Laboratory  of  the  Bar- 
nard Free  Skin  and  Gancer  Hospital  at  St.  Louis. 
There  are  also  a  number  of  foundations  for  the 
study  of  tuberculosis,  such  as  the  Henry  Phipps  Insti- 
tute at  Philadelphia,  the  Trudeau  Foundation  for 
Research  and  Teaching  in  Tuberculosis  at  Trudeau, 
N.  Y.,  the  Research  Department  of  the  National 
Jewish  Hospital  for  Gonsumptives  at  Denver,  the 

[64] 


Kenneth  Dows  Fund  for  the  Study  of  Tuberculosis 
at  the  Johns  Hopkins  Hospital,  etc. 

A  considerable  amount  of  chemical  work  is  done 
at  some  of  these  foundations,  but  it  relates  largely 
to  the  applications  of  chemistry  to  diagnosis  and  to 
problems  in  bacteriology  and  pathology,  although 
some  work  is  done  on  chemo-therapy  and  at  the 
Mayo  Foundation  Kendall  is  doing  his  important 
work  on  thyroxin,  a  very  active  compound  separated 
from  the  thyroid  gland  and  which  can  replace  the 
latter  In  therapeutics. 

The  Dermatological  Research  Laboratories  of  the 
Philadelphia  Polyclinic  have  done  very  Important 
work  on  the  preparation  of  arsphenamlne  and  on 
chemo-therapeutic  studies  with  this  and  other  arsenic 
and  also  mercury  compounds,  as  well  as  on  metabo- 
lism in  certain  skin  diseases. 

The  laboratories  of  the  James  Buchanan  Brady 
Urological  Institute  of  the  Johns  Hopkins  Hospital 
have  made  studies  on  new  antiseptics  of  interest  In 
urology. 

The  Russell  Sage  Institute  of  Pathology ,  In  affili- 
ation with  Bellevue  Hospital,  New  York,  Is  making 
important  calorlmetric  studies  of  the  metabolism  In 
various  diseases. 

J     1    I  In  none  of  the  many  Institutions 

ac    oj .        ^^^^  ^^^^  ^^^^  enumerated,  impor- 

J       1  tant  as  is  their  output  in  research, 

n^   7.    T  hlffhly  needed  as  they  all  are,   Is 

Medical  ^    /.  1     r       ^u 

„    , ,  provision  made  for  the  cooperative 

Problems         ^        ,  ,1  r         j-  •       t« 

attack  on  problems  or  medicine  by 

great  leaders  In  the  fields  of  medicine  and  the  funda- 
mental sciences. 

[65] 


Medical  ,  ^^^   ""^"^y  ^P^"^  annually   on 

Research  in  chemical  work  by  the  United  States 
United  States  Government  runs  into  the  millions. 
Government  ^^^^^^^  ^^^  °^  ^^''^  however,  is  for 
Laboratories  technical  or  economic  purposes  or 
in  connection  with  law  enforcement. 
Only  a  very  small  part  of  it  goes  for  researches  in 
the  lines  under  consideration;  in  fact,  except  for 
some  more  or  less  incidental,  but  very  important, 
work  in  the  Department  of  Agriculture  and  work 
done  by  the  Army  and  Navy  with  special  reference 
to  military  problems,  almost  the  only  research  work 
bearing  directly  upon  the  health  of  man  is  that  car- 
ried on  in  the  Public  Health  Service,  and  especially 
in  the  Hygienic  Laboratory.  In  the  latter  there  is 
a  small  division  of  chemistry  and  also  a  division  of 
pharmacology  in  which  some  chemical  work  is  done. 
In  recent  years  the  chief  activities  of  the  division  of 
chemistry  have  been  directed  to  sanitary  engineer- 
ing; but  now  there  are  prospects  of  some  funda- 
mental work  on  the  metabolism  of  bacteria.  The 
chemical  work  in  the  division  of  pharmacology  has 
been  largely  in  connection  with  the  standards  and 
legal  control  of  drugs,  although  there  has  been  some 
work  on  chemo-therapy  and  on  the  relation  of  chemi- 
cal structure  to  physiological  action;  at  present  chemi- 
cal work  in  connection  with  tuberculosis  is  being 
developed. 

Of  the  present  Government  laboratories  the  Hy- 
gienic Laboratory  would  be  the  best  adapted  for 
development  into  a  medium  cooperative  research 
such  as  that  being  considered.  But  judging  from  the 
past  and  present,  there  seems  little  probability  that 
this  will  occur.    Congress  has  never  made  the  posi- 

166-i 


tions  in  this  laboratory  sufficiently  attractive  from  the 
standpoint  of  salaries  or  of  facilities  and  freedom  for 
work  to  long  retain  the  services  of  chemists  of 
eminence;  in  the  seventeen  years  of  the  existence  of 
this  laboratory  there  have  been  four  chiefs  of  the 
chemical  division  and  the  position  has  been  vacant 
for  about  a  fourth  of  the  time. 

y,        ,  The    appreciation    of    chemical 

Ch      '    IW    k    ^^^^  ^^  ^^^  P^^^  ^^  ^^^  medical 
r  men  of  the  Public  Health  Service 

on  Leprosy  ,  i         r    •  i        • 

and   an   example    or    its   value    m 

public  health  work  were  shown  by  a  recent  report 
from  the  Service's  Leprosy  Investigation  Station 
at  Honolulu  and  Molokai.  The  Director  of  this 
station,  in  discussing  leprosy,  states  that  earlier 
experiments  with  chaulmoogra  oil  indicated  that 
there  is  in  this  oil  "a  most  valuable  curative  agent 
or  active  principle  appealing  to  chemistry  for  its 
isolation,  or,  at  least,  identification'';  and  then 
relates  how,  when  the  cooperation  of  a  chemist  was 
obtained  and  the  ethyl  esters  of  the  acids  of  this  oil 
were  prepared  and  injected  into  lepers  seventy-eight 
of  the  latter  were  cured  of  the  disease.  Such  a  strik- 
ing demonstration  of  the  value  of  the  cooperation 
of  chemists  with  physicians  can  hardly  fail  to  make 
an  impression  on  Congress,  but  it  seems  improbable 
that  any  group  of  chemists  in  the  Government  labora- 
tories will  be  left  free  from  routine  or  law-enforcing 
problems  sufficiently  long  to  accomplish  much  funda- 
mental work.  Public  funds,  moreover,  are  only 
appropriated  for  specific  purposes  and  the  necessary 
freedom  for  work  on  fundamental  principles  would 
therefore  be  practically  impossible  in  a  Government 
institute. 

[67] 


Medical  ^^  ^^  difficult  to  secure  accurate 

Research  in  ^^^^  /^  '^^^'^  ^^  research  work 
Manufacturing  1^^^  '/"  progress  or  contemplated 
Establishments  !^  ^^^dustnal  laboratories,  as  there 
IS  always  a  natural  desire  to  keep 
such  knowledge  from  competitors  until  patents  can 
be  applied  for  or  until  the  products  resulting  from 
the  research,  if  not  patentable,  are  ready  for  the 
market.  Although  a  considerable  proportion  of  the 
drugs  now  in  use  have  resulted  from  researches 
carried  on  in  the  laboratories  of  manufacturing 
establishments,  most  of  this  work  has  been  based 
upon  the  results  of  previous  fundamental  work  in 
universities  or  other  institutions.  Although  many 
pharmaceutical  and  chemical  manufacturers  main- 
tain research  organizations  which  have  been  an 
important  factor  in  reaching  our  present  stage  of 
progress,  no  commercial  establishment  can  maintain 
a  staff  of  specialists  In  the  various  branches  of  science 
such  as  would  be  required  to  accomplish  effective 
work  of  the  character  now  required. 

Ind    trial  ^^^  research  work  of  commer- 

Research  of  ^^^^  ^^^^  ^^^^^  °^  necessity  be  con- 
Great  Value  ^"^^  F^^'^^^y  ^?  ^^^  methods  for 
manufacturing  known  products  and 
to  the  discovery  of  new  substances  through  the  appli- 
cation of  well-established  principles.  Researches  of 
this  kind  are  reasonably  sure  to  develop  Improved 
medicinal  agents  of  the  types  already  In  use,  and  in 
this  way  to  secure  the  financial  returns  necessary  to 
successful  manufacturing  operations.  Such  progress 
is  of  great  value,  as  It  results  In  a  gradual  but  steady 
Improvement  In  medicinal  substances  and  In  building 
up  manufacturing  facilities  and  experience  so  neces- 

[68] 


sary  to  the  complete  development  of  our  chemical 
industry. 

,-       .  The    industries    could    be    very 

Manufacturers     ,    ,    /-  i  i  r     .     •  j 

Would  Assist  '^f 'P^"l  "jy  manufacturing  and  sup- 
plymg  chemicals  required  tor  re- 
search purposes  and  by  carrying  out  operations  on  a 
scale  not  feasible  outside  of  a  well-equipped  factory. 
All  of  the  progressive  chemical  and  pharmaceutical 
manufacturers  would  w^illingly  assist  in  this  manner, 
and  a  number  of  firms  engaged  in  the  manufacture 
of  dyes  and  technical  chemicals  would  also  be  willing 
to  supply  chemicals  and  intermediates  to  be  used  in 
the  preparation  of  medicinal  products.  On  the  other 
hand,  research  of  the  character  contemplated  would 
be  helpful  to  our  chemical  industry,  as  it  would 
stimulate  the  manufacture  of  distinctively  American 
medicinal  products. 

While  we  have  thus  in  the  universities,  in  research 
institutes  and  certain  Government  laboratories  a  con- 
siderable amount  of  most  important  worlc  for  the 
discovery  of  the  cause  and  prevention  of  disease, 
there  is  not  in  a  single  institution  that  cooperative 
effort  of  leaders  in  the  field  of  organic  chemistry, 
physical    chemistry,    pharmacology    and    medicine. 

Isolation  Bars     ,   ^^^.    ^^°'''*.   ^"i^    '^°'f«'^-    .  "^e 
p  have  in  one  institute  the  eminent 

pathologist  with  chemical  assis- 
tance, but  lacking  the  constant  full-time  cooperation 
of  leaders  in  synthetic  organic  chemistry,  in  physical 
chemistry,  in  pharmacology.  In  another  institute  a 
great  chemist  may  be  working,  but  his  brother 
chemist,  the  leader  in  physical  chemistry,  and  the 
great  pharmacologist,  are  lacking.  There  is  thus 
no  single  institute  in  w^hich  the  whole  effort  is  based 
on  the  joint  attack  on   fundamental  problems   of 

[69] 


medicine  by  leaders  in  chemistry,  physics,  pharma- 
cology and  medicine. 

Foreign  Institutes  and  Laboratories 

jif  ^'    I  Of    the    institutes    in    Germany 

r.  ,  .         where  the  applications  of  chemistry 

Kesearcn  m  ,  /•    v  i-    / 

P  to  the  cure  or  disease  are  studied, 

the  Institute  for  Experimental 
Therapy  at  Frankfort  is  probably  the  best  known. 
This  Institute  was  founded  in  1899,  in  recognition 
of  Ehrlich's  services  in  standardizing  diphtheria  anti- 
toxin^ and  making  it  a  much  more  practical  remedy. 
The  name  "Institute  for  Serum  Investigation"  was 
at  first  proposed,  but  Ehrlich  requested  that  no  such 
limitation  be  placed  upon  its  scope.  It  was  not, 
however,  until  1906  that  Ehrlich  realized  his  hopes 
of  being  able  to  work  in  continuous  close  cooperation 
with  chemists ;  this  was  made  possible  by  the  found- 
ing and  endowment  by  Frau  Speyer  of  the  George 
Speyer  House,  an  integral  part  of  the  Institute,  but 
devoted  exclusively  to  chemical  research  in  con- 
nection with  biological  and  especially  therapeutic 
problems. 


'  It  Is  an  interesting  and  apparently  unwritten  bit  of  history  that 
Ehrlich  was  in  part  led  to  his  important  work  on  diphtheria  anti- 
toxin by  endeavors  to  analyze  the  toxic  action  of  cocaine;  it  had 
been  reported  that  the  "toxalbumins,"  ricin  and  abrin,  produced 
lesions  in  the  liver  similar  to  those  he  had  seen  from  the  "toxo- 
phore"  group  of  cocaine;  he  repeated  the  experiments  with  ricin 
and  abrin  and  discovered  that  antitoxins  are  formed  which  neu- 
tralize these  toxins  in  the  test  tube,  and  that  the  strength  of  the 
antitoxin  may  be  determined  in  this  way.  Up  to  that  time  it  had 
been  generally  believed  that  antitoxins  could  neutralize  the  effects 
of  toxins  only  indirectly  through  some  obscure  action  upon  living 
tissues,  and  a  cumbersome  and  unreliable  method  of  standardizing 
diphtheria  antitoxin  was  in  use.  It  was  largely  as  a  result  of  these 
studies  of  Ehrlich  that  diphtheria  antitoxin  became  such  a  trust- 
worthy remedy. 

[70] 


_,,   ,.  ,  ^  „  Ehrlich    at   once    increased   the 

Ehrlich  Calls  i      r^u      t     ^-^  ^      /     u-u 

,       .  personnel  of  the  Institute    (which 

already  included  bacteriologists, 
pathologists  and  immunologists)  by  securing  not 
only  organic  chemists,  but  physical  and  biological 
chemists,  protozoologists,  etc.  The  result  of  the 
combined  efforts  of  this  group  was  the  discovery  of 
arsphenamine  ("606") .  Much  work  was  also  done 
upon  the  chemo-therapy  of  cancer,  sleeping  sickness, 
malaria,  etc.,  and  important  studies  have  been  made 
on  new  classes  of  germicides  (with  the  hope  of  find- 
ing one  which  will  kill  or  inhibit  bacteria  in  the  hu- 
man body),  on  quinine  derivatives,  the  therapeutic 
value  of  dyes,  etc. 

Since  Ehrlich's  death  the  work  has  been  con- 
tinued (with  Kolle  as  director)  along  both  chemo- 
therapeutic  and  immunological  lines,  and  notwith- 
standing the  greatly  reduced  budget  and  personnel 
as  a  result  of  the  war,  important  results  have  been 
obtained. 

E»    7.     D      -  The    success   of   the    Frankfort 

Berlin  Boasts  ^       .  1        •       1        j    1 

^        ,  ^  Institute  apparently  stimulated  the 

Complete  r         1     •  r  1  1 

T    ^'^  ^  toundation  or  analogous  research 

Institute  .       .  .       /-.  ^T^i  • 

institutes    in    Germany.       1  nus    in 

191 1  there  was  founded  by  private  subscription  and 

endowment  at  Berlin-Lichterfelde  another  Institute 

for  Experimental  Therapeutics  (the  Kaiser  JVilhelm 

Institut  fiir  experimentelle  Therapie)  ^  w4th  Wasser- 

mann,  a  pupil  of  Ehrlich,  as  director  and  Neuberg  in 

charge  of  bio-chemistry.     This  is  one  of  the  most 

completely  equipped  institutes  in  the  world,  and  is 

near  a  similar  Institute  for  Chemistry  and  also  one 

for  Biolog}'  and  not  far  from  the  Pharmaceutical 

Institute.    It  w^as  planned,  before  the  war,  to  found  a 

similar  research  institute  for  physiology.    One  of  the 

[71] 


subjects  to  which  special  attention  is  devoted  is  the 

metabolism  of  bacteria,  which  is  the   fundamental 

basis  for  the  treatment  of  bacterial  infections. 

J  ri'  '  '        I         A   division   for   chemo-therapy, 
A  Division  of     .        , ,.  .  ,        ,        ,         .    r-'' 

^,         rp,  m  addition  to  the  already  existing 

L nemo- 1  her apy     ,.    •  •  r      i        •  i  i 

division    or    chemistry,    has    been 

added  to  the  Robert  Koch  Institute  for  Infectious 

Diseases,  at  Berlin,  and  placed  under  the  directorship 

of  Morgenoth,  one  of  Ehrlich's  most  distinguished 

pupils  and  the  discoverer  of  the  action  of  ethylhydro- 

cupreine,  a   derivative   of  quinine  having  a  highly 

specific  action  on  the  pneumococcus  and  of  value  in 

treating  local  infections  due  to  this  organism. 

It  is  interesting  to  recall  that  in  this  Institute 
(which  was  founded  by  the  Prussian  Government 
for  Koch  in  1891 )  a  large  amount  of  work  was  done 
by  Koch,  von  Behring,  Ehrlich,  Brieger,  and  others 
on  the  chemical  nature  of  bacterial  toxins  and  anti- 
toxins and  in  a  search  for  germicides  which  would 
destroy  bacteria  in  the  body.  The  discovery  of  the 
antitoxins  for  diphtheria  and  tetanus  diverted  the 
studies  toward  immunity,  but  Ehrlich  always  held  to 
the  belief  that  such  germicides  would  be  discovered 
and  after  spending  nearly  ten  years  in  studies  on 
immunity  was  convinced  that  the  prospects  for  over- 
coming most  infectious  diseases  by  the  use  of  definite 
chemical  compounds  were  brighter  than  those  for 
discovering  new  antitoxins,  etc.  Now,  after  nearly 
thirty  years,  Morgenoth  has  again  taken  up,  in  the 
same  institute,  these  earlier  lines  of  work  of  Koch 
and  Ehrlich  and  is  obtaining  encouraging  results. 

Ample  facilities  for  the  study  of  chemical  com- 
pounds in  connection  with  the  cure  of  disease  have 
been  provided  in  the  comparatively  new  (about 
1907)     and    most    elaborate    laboratories    of    the 

[72] 


Imperial  Health  Office  at  Berlin  and  Dahlem.   Some 

of  the  earliest  and  most  important  work  on  the  study 

CT,  ,  of    arsenic    compounds    in    experi- 
tilaborate  ,  i  -i-  i     i        •  •  i 

^  ,  mental  syphilis  and  sleeping  sick- 

Government  -^  ^i  ,  .        T  Tl  1       1        1 

r   ,  .         ness  was  done  here  by  Uhlenhuth. 

Laboratories       rr-i  •        rr        i  i        •     i       i 

1  his  omce  has  chemical,  pharma- 
cological, zoological,  hygienic  and  bacteriological 
laboratories. 

The  Prussian  Government,  in  1895,  established  in 
connection  with  the  University  of  Marburg  an  Insti- 
tute  for  Hygiene  and  Experimental  Therapy,  and 
placed  it  under  the  directorship  of  von  Behring.  The 
work  of  this  institute  has  in  recent  years  dealt  largely 
with  processes  of  immunization  to  diphtheria  and 
tuberculosis,  but  a  large  amount  of  work  on  chemical 
antiseptics  has  also  been  done.  Chemical  studies 
played  a  large  part  in  von  Behring's  work  on  the 
antitoxins;  he  obtained  his  first  antitoxins  by  the  use 
of  cultures  and  toxins  the  virulence  of  which  had 
been  lessened  by  the  action  of  chemical  reagents.  In 
fact,  just  as  Ehrlich  was  led  to  some  of  his  most 
important  work  on  immunity  by  his  pharmacological 
studies,  so  von  Behring  arrived  at  the  conception  of 
"soluble  toxins"  (which  led  to  the  discovery  of  anti- 
toxins) from  his  endeavors  to  explain  the  toxic  action 
of  iodoform  and  also  its  beneficial  action  in  the  heal- 
ing of  wounds. 

There  are  also  in  Germany  many  laboratories  and 
institutes  devoted  to  the  study  of  special  diseases  in 
which  considerable  chemical  work,  from  the  stand- 
point of  treatment,  is  done.  Thus  important  work 
in  chemo-therapy,  especially  in  relation  to  malaria 
and  sleeping  sickness,  is  being  done  in  the  Institute 
for  Naval  and  Tropical  Diseases  at  Hamburg,  in 
which  a  special  Chemical  Division  for  such  work  has 
been  established. 


,    ,.    ,     /  The  Charite  Hospital  at  Berlin 

Institutes  for      ^  ^    .        .       , 

C  Stud  many    years    maintained    an 

Institute  for  the  Study  of  Cancer; 
it  was  founded  originally  for  the  study  of  the  cause  of 
this  disease.  Then  for  a  number  of  years  the  activi- 
ties were  directed  toward  chemo-therapy;  Emil 
Fischer  cooperated  in  this  work  and  had  a  large  num- 
ber of  new  chemical  compounds  prepared  which  were 
tested  for  possible  therapeutic  effects.  More  re- 
cently the  scope  of  the  work  has  been  enlarged  and 
such  problems  as  the  biology  of  plant  tumors  have 
been  taken  up.  There  is  also  an  Institute  for  the 
Experimental  Study  of  Cancer  at  Heidelberg  and  a 
Division  for  the  study  of  this  disease  in  the  Frank- 
fort Institute  for  Experimental  Therapy;  in  both  of 
these  considerable  chemical  work,  from  the  stand- 
point of  treatment,  has  been  done. 

Much  valuable  work  continues  to  be  done  by  the 
University  Institutes  of  Pharmacology,  for  unlike 
the  situation  in  this  country,  all  of  the  German  uni- 
versities have  for  many  years  supported  large  inde- 
pendent departments  of  pharmacology.^ 

The  only  noteworthy  French  institutes  for  medical 
and  biological  research  are  the  Pasteur  Institute  at 
Paris  and  the  analogous,  but  smaller,  Pasteur  Insti- 
tutes at  Lille  and  Tunis.  The  Paris  Pasteur  Insti- 
tute (founded  by  public  subscription  in  1885  for  the 
prevention  and  treatment  of  rabies)  consists  at 
present  of  three  institutes :  bacteriological,  serothera- 

^  The  same  was  true  of  the  universities  of  Austria,  Hungary, 
Russia,  Sweden,  Norway  and  Switzerland;  and  Holland  has  re- 
cently established  pharmacological  institutes  at  all  of  the  Univer- 
sities where  they  were  not  already  present.  The  leading  veterinary 
schools  of  Germany,  Austria  and  Hungary  also  had  independent 
chairs  and  institutes  of  pharmacology.  In  fact  there  were  about 
as  many  real  departments  of  pharmacology  in  these  veterinary 
schools  as  there  are  in  the  medical  schools  in  the  United  States 
at  present. 

[74] 


ji/f  J-    I  peutic  and  biochemical,  each  with  a 

Medical  ^      ,           .      ,  j-    •  .             -ri      i  • 

„          ,    .  number  of  subdivisions.     Ihe  bio- 

Research  m  .        .     ,   .       .           ,          v   .  .            r 

p  chemical  institute  has  divisions  or 

biological  chemistry,  physical  chem- 
istry and  **therapeutlc  chemistry." 

A  large  amount  of  biochemical  work  has  been 
done,  especially  by  Bertrand  and  his  co-workers,  on 
glucosldes,  enzymes,  the  occurrence  of  manganese, 
boron,  etc.,  in  nature  and  the  effects  of  certain  chemi- 
cals upon  the  biological  activities  of  bacteria.  Many 
physical  chemical  studies  relating  to  biological  prob- 
lems have  been  carried  on  in  the  division  of  physical 
chemistry.  In  the  division  of  therapeutic  chemistry 
much  work  has  been  done  on  alkaloids,  amines, 
chlorine  derivatives,  and  other  compounds  of  phar- 
macological interest;  also  Important  work  on  the 
relation  of  chemical  structure  to  physiological  action ; 
the  chemistry  of  a  number  of  arsenic  and  mercury 
compounds  of  Interest  in  the  treatment  of  syphilis 
and  sleeping  sickness  and  a  long  series  of  studies  on 
local  anaesthetics  from  which  the  discovery  of 
"stovaine"  resulted. 

Many  of  the  men  at  the  Pasteur  Institute  are 
"part-time"  men,  holding  also  teaching  or  research 
positions  in  educational  or  other  institutions.  In 
fact  It  Is  difficult  to  determine  how  much  of  the  work 
mentioned  above  should  be  credited  to  the  Institute 
and  how  much  to  other  Institutions. 

Probably  the  Laboratories  in  England  which  have 
done  the  most  cooperative  work  on  the  relations  of 
chemistry  to  physiology  and  pharmacology  are  the 
Wellcome  Physiological  and  the  Wellcome  Chemical 
Research  Laboratories,  located,  respectively,  at 
Heme  Hill  and  Snow  Hill,  London.     These  w^ere 

[75] 


^   ,.    ,  established  in  1894  by  H.  S.  Well- 

r,  ,    .        come,  of  the  firm  Burroughs,  Well- 

Research  m  or-       u  ^  ^u     •         ..•      i.- 

F    I  nd         come  &  Co.,  but  the  mvestigations 

conducted  in  them  have  been  prac- 
tically entirely  separated  from  the  commercial  in- 
terests of  this  firm. 

In  the  physiological  laboratory  the  pharmacolo- 
gists Dale,  Laidlaw,  and  others  and  the  chemists 
Barger,  Walpole,  Ewins,  Carr,  and  others  made 
many  important  contributions  to  the  relations  be- 
tween drugs  and  certain  parts  of  the  nervous  sys- 
tem; the  isolation  and  pharmacological  study  of 
active  amines  from  putrid  meat,  ergot  and  other 
sources  and  the  determination  of  the  constitution  and 
the  synthesis  of  some  of  them ;  very  important  stud- 
ies on  anaphylaxis,  the  pituitary  gland,  on  esters 
and  ethers  of  choline,  etc.,  as  well  as  many  studies 
of  more  purely  chemical  or  physiological  interest. 
This  laboratory  has  also  cooperated  on  a  number  of 
problems  with  the  chemists  of  the  Wellcome  Chemi- 
cal Research  Laboratory  (for  example  on  the  syn- 
thesis of  substances  allied  to  epinephrine)  and  with 
the  chemists  of  the  Wellcome  Works  (for  example 
on  the  relation  between  chemical  constitution  and 
physiological  action  of  large  groups  of  alkaloids 
and  other  organic  compounds) .  In  the  Wellcome 
Chemical  Research  Laboratory  important  work  of 
biological  interest  was  done  on  many  compounds  re- 
lated to  atrophine,  epinephrine,  etc.,  and  chemical 
examinations  of  many  plants  of  reputed  therapeutic 
value  made;  among  the  latter  may  be  mentioned  a 
study  of  the  fatty  acids  of  chaulmoogra  oil,  the  esters 
of  which  are  now  proving  of  so  much  value  in  the 
treatment  of  leprosy. 

Many  changes  in  the  personnel  of  these  labora- 
[76] 


tories  occurred  just  before  and  during  the  war,  and 
whether  the  work  will  be  carried  on  in  the  future  on 
the  same  scale  seems  doubtful. 

Eneland  to  Some  of  the  former  members  of 

Studv  ^^^    physiological    laboratory    are 

Chemo-Medical   ^ow  inaugurating  somewhat  similar 
P    hie  work  m  the  department  of  phar- 

macology and  biochemistry  of  the 
newly  organized  Ministry  of  Health,  in  which  plans 
have  been  made  for  the  extensive  prosecution  of 
studies  on  the  relations  of  chemistry  to  biological 
and  medical  problems. 

Of  other  laboratories  and  institutions  In  England 
in  which  studies  on  the  applications  of  chemistry  to 
biological  and  medical  problems  are  conducted  may 
be  mentioned  the  Lister  Institute  of  Preventive 
Medicine  (founded  in  1891  for  somewhat  the  same 
purposes  as  the  Pasteur  Institute),  In  which,  in  addi- 
tion to  the  work  on  problems  of  Immunity,  serum 
therapy,  etc.,  some  fundamental  studies  on  the  action 
of  antiseptics,  and,  more  recently,  a  very  comprehen- 
sive study  of  the  vltamlnes  have  been  made;  the 
Liverpool  School  of  Tropical  Medicine,  and  its  al- 
lied laboratories,  where  pioneer  work  was  done  on 
the  treatment  of  sleeping  sickness  with  arsenicals; 
the  Imperial  Cancer  Research  Fund  and  the  Cancer 
Research  Laboratories  of  the  Middlesex  Hospital, 
Most  of  the  Universities  of  England  and  Scotland 
have  well-equipped  departments  of  pharmacology  In 
which  much  valuable  work  Is  being  done. 

...  The  leading  institute  for  medi- 

P        ^,    .        cal  research  In  Japan  Is  the  Kita- 

J  sato  Institute  for  Infectious   Dis- 

japan  gases.     This  was  established  as  a 

private  foundation  in  1892  by  Koch's  pupil  and  co- 

[77] 


worker  Kitasato,  and  was  modeled  after  the  Prus- 
sian Institute  for  Infectious  Diseases;  it  was  soon 
taken  over  by  the  Government,  but  in  19 14  was 
enlarged  and  became  again  a  private  institute.  A 
division  of  chemo-therapy  was  added  and  placed  in 
charge  of  Hata,  the  associate  of  Ehrlich  in  the  dis- 
covery of  "606." 

The  Universities  of  Japan  have  departments  of 
pharmacology  which  seem  to  be  at  least  the  equal  of 
those  in  this  country. 


[78] 


CONCLUSION 

Every  single  change  of  every  living  organism  Is 
unquestionably  chemical  and  physical  in  its  funda- 
mental character,  but  the  organism  as  a  whole  is  still 
far  beyond  the  scope  of  the  chemist  and  physicist. 
No  one  has  converted  lifeless  into  living  matter 
without  the  aid  of  life  itself.  We  have  in  life  a  mar- 
velously  organized  system  for  coordinated,  highly 
complex  physical  and  chemical  reactions  which  are 
in  a  normal  condition  largely  self-regulating.  With 
all  the  advances  of  exact  science,  it  will  probably  be 
beyond  the  power  of  man  to  duplicate  life's  organi- 
zation, even  In  its  lowest  and  simplest  forms,  for 
many,  many  generations  to  come.  We  still  must 
adhere  to  the  profound  advice  of  Bacon:  "Nature 
is  to  be  commanded  only  by  obeying  her." 

Every  single  biological  change,  in  health  and  In 

disease,   is  in   turn   fundamentally  a   chemical   and 

physical  process,  subject  to  the  rigorous,  exact  laws 

of  chemistry  and  physics. 

r  •/       jTt    ui.        The  problems  of  life  and  health, 
Life  and  Health  .  ^        111  j.  •  • 

n  JO-  as  sareguarded  by  medicme,  are  m 

Uemand  bcience    ,    .       °  •'  .         . 

r^  ..  ,  their  very  nature  so  complex  that 

Cooperation  •  1  r  1       1  1  1 

rapid  successful  advance  demands 

the  cooperative  effort  of  scientists  of  the  highest  type, 

each  a  leader  in  his  field  and  deeply  Interested  In  the 

correlated   fields   of   science,   willing  to   merge   his 

talents  and  his  effort  in  the  common  problem  for 

the  common  good. 

[79] 


A  fundamental  attack  on  the  problem  of  the  more 
successful  preservation  of  health  and  cure  of  disease 
demands  the  cooperative  effort  of  the  chemist,  the 
physicist,  and  those  experts  In  the  fields  of  biology 
who  are  most  Immediately  concerned  with  the  scien- 
tific study  of  disease,  namely,  the  pathologist,  who 
studies  the  changes  In  the  organisms  produced  by 
disease,  the  bacteriologist,  student  of  our  chief  ene- 
mies, the  microorganisms  or  disease  germs,  and  the 
pharmacologist,  who  investigates  the  effects  of  drugs 
of  all  kinds  on  the  organism. 

The  biologist  —  pathologist,  bacteriologist,  or 
pharmacologist — would  be  wholly  at  a  loss  in  a 
thoroughgoing  effort  to  chart  the  seas  of  disease  and 
health  without  the  aid  of  the  chemist  and  physicist 
to  study  minutely  and  exhaustively  those  chemical 
and  physical  questions  which  form  the  very  breath 
of  life. 

^,       .  ^        J        Medical  Investigators  are  return- 
Lhejnistry  ana    .  ,  .         .  .         ^  i 

PA  •  N  ^  ^  ^^S  to  the  universities  for  the 
study  or  more  chemistry  and  more 
physics.  Others  are  planning  to  have  their  sons 
study  chemistry  and  physics  exhaustively  before 
turning  to  the  study  of  medicine.  There  are  great 
biologists  who  have  devoted  years  of  study  to  the 
fundamental  sciences  with  a  great  measure  of  suc- 
cess. These  are  but  evidences  of  the  widespread 
recognition  of  the  path  that  promises  the  greatest 
measure  of  progress  in  medicine. 

But  with  the  tremendous  fields  covered  by  each 

Individual  science — biology,  pathology,  bacteriology, 

P  ..         .  pharmacology,   physics,   organic 

Effort  a  War      chemistry,  physical  chemistry— it  is 

r  evident  that  greater  advances  can 

Lesson  ,  ,  •  n  i 

be  made,  more  rapidly  and  more 

[80] 


certainly,  by  the  cooperativ^e  effort  of  congenial  men. 

This  was  the  lesson  of  the  war;  it  must  be  the  lesson 

of  peace.     It  will  fall  to  the  lot,  therefore,  of  the 

thoroughly  trained  chemist  and  the  leader  in  physics, 

by  minute  analysis  of  substance  and  function,  and  by 

the  application  of  the  methods  of  synthesis,  to  supply 

to  the  biologist  that  exact  knowledge  of  the  units  and 

forces  from  which  the  complex  whole  is  elaborated, 

which  will  ultimately  raise  medicine  from  the  level 

of  an  art  to  the  higher  level  of  an  exact  science  of 

healing  and  preservation  of  health. 

.       .      T     1  We  have  in  this  country  a  num- 

America  Lacks  .  .  .,  ... 

^  ..  .  ber  or  excellent  research  mstitutes 

Cooperative  ,  ,  t     i   •  .       . 

n  1  devoted  to  medical  mvestigations, 

with  staffs  of  the  highest  calibre. 
It  must  be  said,  however,  without  fear  of  contradic- 
tion, that  there  is  not  a  single  organization  whose 
purpose  is  a  determined  cooperative  attack  on  the 
problems  of  disease  and  health,  where  intense  chemi- 
cal and  physical  research  goes  hand  in  hand  with  the 
medical  and  biological  study  of  disease.  The  impor- 
tance of  chemistry  and  physics  has  been  recognized, 
but  the  direction  of  research  is  still  essentially  in  the 
hands  of  medical  men.  No  one  of  the  scientific 
groups  alone  should  be  entrusted  with  leadership. 
All  are  needed  for  coping  successfully  with  the  com- 
plex and  formidable  problems.  Complete  coopera- 
tion of  a  staff  of  experts,  peers  in  every  sense,  each 
in  his  own  field,  with  emphasis  on  the  fundamental 
chemical  and  physical  character  of  the  problems,  has 
nowhere  been  accomplished.  Consequently  it  is  pro- 
posed that  the  attack  be  actually  cooperative,  from 
the  selection  of  the  problem  and  the  formulation  of 
the  plan  of  work  through  the  whole  concentrated 
effort  to   grapple   with   Nature   and   ultimately  to 

[81] 


conquer  outpost  after  outpost  of  the  complex  world 
of  life. 

May  the  day  come  when  the  lesson  of  the  power 
of  cooperative  scientific  endeavor,  so  effectively  util- 
ized in  the  Chemical  Warfare  Service  organization, 
may  be  applied  with  equal  success  to  the  solution  of 
the  problems  of  disease  and  health. 


[82] 


Discussion  Promotes 
Progress 

Members  of  the  committee  who 
prepared  the  report  will  welcome 
and  appreciate  criticism  or  sugges- 
tions from  its  readers.  It  is  hoped 
that  the  fullest  discussion  of  this 
subject  may  be  entered  into  through 
the  medical  societies,  the  medical 
journals,  the  press  and  other  me- 
diums. 


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